This study was aimed to prepare polyherbal formulations for weight loss considering six herbs: Allium sativum, Plantago ovata, Nigella sativa, Carum copticum, Trigonella foenum-graecum and Syzygium aromaticum. This study was carried out in five phases: Preparation and formulation, Pharmacological and biological activities, Phytochemical investigations, efficacy trial on animals (rabbits and guinea pigs) and human trials. Irradiation was performed using “Cobalt 60” (dosages of 10 and 5 kGy) as the source on polyherbal formulations for shelf life extension before using in efficacy trial. Crude methanolic extract (Crd. MeOH Ext.) and different fractions of all selected plants were investigated for various pharmacological and biological activities including, antibacterial, antifungal, phytotoxic and insecticidal. The pharmacological / biological investigations revealed that C. copticum possesses significant antifungal activity in Crd. MeOH Ext. against Trichoderma harzianum (91%), while Crd. MeOH Ext. of S. aromaticum showed significant activity against Penicillium oxalicum (85%), chloroform (CHCl3) extract of A. sativum showed significant activity against Verticillium lecanii (87%), Crd. MeOH Ext. of N. sativa showed significant antibacterial activity against Escherichia coli (89%), Proteus mirabilis (96%), Bacillus cereus (89%) and Xanthomonas oryzae (88%). The plant materials showed significant phytotoxic effects against Lemna minor at higher concentrations; Crd. MeOH Ext. of N. sativa showed good growth regulation (75%) at 1000 µg/mL, moderate growth regulation (50%) at 100 µg/mL and low growth regulation in aqueous fraction (30%) at 10 µg/mL concentrations;Crd. MeOH Ext. of A. sativum, C. copticum and S. aromaticum showed significant insecticidal activity (90, 90 and 100%, respectively) against Tribolium castaneum. The phytochemical investigations showed that the quantity of tannin (0.54 mg/100 g), alkaloids (0.45 mg/100 g) and flavonoids (0.058 mg/100 g) was increased by the use of irradiations while vitamin C showed a slight decrease of 5 mg/100g. Efficacy trials on animals showed decrease in body weight and cholesterol level, while increased serum glutamic transaminase (SGPT) level. The alkaline phosphatase and bilirubin levels were normalised by the use of polyherbal formulations. Haemoglobin and platelets were increased in number, while monocytes, eosinophil, neutrophils and lymphocytes remained unchanged in both rabbits and guinea pigs. Human efficacy trials by use of polyherbal formulations for a period of two months exhibited decrease in body weight, body measurements, low density lipoprotein (LDL), alkaline phosphatase, fasting glucose and total cholesterol levels, while increase was observed in platelets count, haemoglobin level and high density lipoprotein (HDL) level. No changes were reported for monocytes, eosinophil, neutrophils and lymphocytes counts. For shelflife extension, the polyherbal formulations were exposed to different irradiation doses of 10 and 5 kGy (source: Cobalt 60) and then compared with un-irradiated samples. In this case, same results were found. Statistical package for social sciences (SPSS) version 16 was used for the calculation of results; two-way, one-way ANOVA and chi-square tests were used (P< 0.05).