Natural products based drug discovery is still a challenging area for the exploration of new lead compounds. The present research project aims to scientifically validate the folkloric use of selected plants (Tamarix aphylla, Tamarix dioica, Acacia cyanophylla and Acacia stenophylla) in pain and inflammation. Phytochemical screening showed the presence of alkaloids, carbohydrates, saponins, terpenes, flavonoids, tannins, anthraquinones and amino Acids in crude methanolic extract of Tamarix aphylla, Tamarix dioicaand Acacia stenophylla, while Tamarix aphylla showed negative result for steroids, glycosides and sterols. The crude extract ofAcacia cyanophylla showed positive test results for alkaloids, carbohydrates, saponins, cholesterol, flavonoids, steroids, anthraquinones, terpenes, sterols and tannins. The crude extracts of Tamarix aphylla, Tamarix dioica, Acacia cyanophylla and Acacia stenophylla stem bark were screened for fatty Acids. Experimental data showed that all of the four plants contained different concentrations of various fatty Acids. Major fatty Acid in all the studied plant samples was Linoleic Acid; its concentration was 0.11%, 0.41%, 0.22% and 012% in Tamarix aphylla, Tamarix dioica, Acacia cyanophylla and Acacia stenophylla respectively. Linoleic Acid was followed by Palmitic Acid (0.04%) in Tamarix aphylla, Octadecadienoic Acid in Tamarix dioica, Acacia cyanophylla (0.12% and 0.10% respectively) and gamma-linolenic Acid (0.08%) in Acacia stenophylla. The crude methanolic extracts of Tamarix aphylla, Tamarix dioica, Acacia cyanophylla and Acacia stenophylla obtained from stem bark were screened for various biological/ pharmacological activities. Our results declared that all the four plants demostrated good antimicrobial activity at the concentration of 2mg disc-1 against the tested microbes. Among the tested plants, highest zone of inhibition was shown by Tamarix aphylla (81.25 %) against Bacillus atrophus (gram positive). Similarly, highest antifungal activity was shown by Acacia cyanophylla against Candida albican (72.22%). In case of antioxidant activity, the crude extracts of Tamarix aphylla, Tamarix dioica, Acacia cyanophylla and Acacia stenophylla possessed good antioxidant activity of 831, 976, 1153 and 1467 (IC50) respectively. The plant extracts also showed enzyme inhibitory activity. Acetylcholinesterase was inhibited by Acacia cyanophylla and Acacia stenophylla only. Maximum inhibitory activity was demonstrated by Acacia stenophylla (37.11μg/ml) in Ethyl acetate fraction, and minimum inhibition was shown by aqueous fractions (91.46μg/ml) of Acacia cyanophylla. The results revealed that maximum Lipoxygenase inhibitory activity was shown by Ethyl acetate extracted sample of Tamarix aphylla which was 27.3μg/ml, minimum was recorded for aqueous fraction of Acacia stenophylla (142.3μg/ml). Similarly, the crude methanolic extracts of all the four plant species possessed significant anti-inflammatory, analgesic and antipyretic activity at all doses. The results revealed that the analgesic activity of the crude methanolic extract of different plant species when measured by acetic Acid model was dose dependent and the increasing concentration of the extract increased its activity. Maximum activity of 66.19% was shown by Acacia stenophylla at the dose of 400 mg/kg followed by Tamarix dioica (64.33%) at the same dose. The analgesic activity conducted by Hot Plate method indicated that the same activity was dose and time dependent. Maximum activity of 54.49% was achieved by Tamarix aphylla, when the mice were exposed to 90 minutes at higher dose of 400 mg/kg. Similarly, minimum analgesic activity by the same assay was measured in case of Acacia stenophylla (11.22%) at a dose of 200 mg/kg. Our data also indicated similar pattern for antipyretic activity as was observed for analgesic activity. Tamarix aphylla revealed maximum inhibitory activity at the higher dose of 300 mg kg-1 during the 3rd hr, while minimum activity was noted for Acacia stenophylla (0.02%) at lower dose of 100 mg/kg exposed to the 1st hour. Anti-inflammatory activity evaluated by Carageenan-Induced Paw Edema and Xylene-Induced Ear Edema Model revealed that anti-inflammatory activities were dose and time dependent. Maximum anti-inflammatory activity (54.12%) was shown by crude methanolic extract of Tamarix dioica at a dose of 200 mg kg-1 after 5 hours on Carrageenan-Induced Paw Edema Model. Tamarix dioica was followed by Tamarix aphylla (51.84%). Similarly, anti-inflammatory effect assessed via Xylene-Induced Ear Edema Model revealed that maximum effect of 68.80% was demonstrated by Acacia cyanophylla at the dose of 200 mg/kg after 60 minutes. It was followed by Tamarix aphylla (68.59%). Minimum inhibitory effect was shown by Tamarix dioica which was 32.29% at lower concentration of 50 mg/kg when the tested animals were exposed for 15 minutes. All plants were screened for acute in-vivo toxicity using albino mice and no considerable toxicity was observed up to the dose of 2000 mg/kg. This study explicitly validated folk uses of the selected plants (Tamarix aphylla, Tamarix dioica, Acacia cyanophylla, Acacia stenophylla) in various diseases. Furthermore, this data indicate the strong potential of all these plants for isolation and identification of new bioactive compounds for better management of respective diseases.