The aim of this study was to prepare and evaluate the impact of polymers on fabricating stable dexibuprofen (Dexi) and domperidone nanocrystals with enhanced therapeutic potential, using a low energy, anti-solvent precipitation method (APSP). Combinations of Hydroxypropyl methyl cellulose-Polyvinyl pyrrolidone and Hydroxypropyl methyl cellulose-Eudragit were shown to be very effective in producing stable dexi-nanocrystals with particle sizes of 85.0±2.5 nm and 90±3.0 nm, and polydispersity of 0.179± 0.01, 0.182± 0.02 respectively. Produced nanocrystals of DOMP and Ethucel combination, the average particle size and polydespersity index were found to be approximately 130.00 ± 3.0 nm, 0.15 ± 0.01, moreover, the combination of hydroxyl propyl methyl cellulose and polyvinyl alcohol also found very affective to produce DOMP nanocrystals with small particle size (200.0 ±3.5nm) and PDI (0.2±0.02). The stability studies conducted for 90 days demonstrated that nanocrystals stored at 2-8°C and 25°C were more stable than those at 40°C. The maximum recovery of dexi-nanocrystals was observed from the formulations using the combination of Hydroxypropyl methylcellulose- Polyvinyl pyrrolidone and Hydroxy propyl methyl cellulose- Eudragit, which equated to98% and 94% of the nominal active drug content respectively. In case of DOMP nanosuspensions stored at 2-8 ºC and room temperature (25 ºC) exhibited higher stability compared to the samples stored at 40 ºC. Crystallinity of the processed and unprocessed dexi and DOMP particles was confirmed using Differential Scanning Calorimetry, Powdered X-ray Diffraction and Transmission Electron Microscope. FTIR studies for both Dexi and DOMP nanocrystals confirmed that the process did not affect chemical integrity of DOMP. The DOMP nanoparticles exhibited significantly enhanced dissolution rate (P<0.05) compared to the raw counterpart. The saturation solubility of the ix dexinanocrystals was substantially increased to 270.0±3.5 µg/mL compared to the raw dexi in water (51.0± 2.0μg/mL) and stabilizer solution (92.0 ± 3.0 μg/mL). Enhanced dissolution rate (P<0.05) was observed for the dexi-nanocrystals compared to the unprocessed drug substance and marketed tablets. The saturation solubility of the DOMP nanocrystals was significantly increased to 2700.0± 3.5 µg/mL compared to the raw dexi in water (952.0± 2.0μg/mL) and stabiliser solutions which include HPMC (1253.0± 3.5) and HPMC-PVA (1133.0 ± 3.5 µg/ml). DOMP nanocrystals resulted in enhanced dissolution rate (P<0.05) compared to the unprocessed drug substance. Molecular Modeling studies underpinned and substantiated the experimental studies, including the impact of polymers on nanoparticle sizes, nanocrystals recovery and stability studies of the produced dexinanocrystals. The highest potential was shown by combination ofHPMC-PVP- Dexi (-4.7) and HPMC EUD- DEXi (-4.6) . In case of DOMP, Molecular Modelling studies underpinned the molecular level understanding of the DOMP-Polymer nanocrystal interaction and substantiated the experimental studies, including the impact of polymers on nanocrystals sizes, and stability studies of the produced DOMP nanocrystals. Ethocel as single polymer showed highest binding potential (-27.26±0.24 ) for DOMP nanocrystals and HPMC-PVA was found the best dimer to effectively bind (-25.22 ± 0.79) with the nanocrystals with subsequent small particle size and high stability profile. The findings of the nociceptive assay showed that the dexinanocrystals exhibited significant analgesia, compared to the raw dexibuprofen and the control standard diclofenac sodium. The analgesic effect was, however, produced at much lower doses (5mg/kg) than that of control standard, diclofenac sodium (20mg/kg) and dexibuprofen counterparts (40 mg/kg). While theactivity results in anti-emetic assay confirmed that the nano-formulation provided significant anti-emetic effect (P< 0.05) x at a dose of 0.5 mg/kg, comparable to that of the unprocessed DOMP and the control standard Metoclopramide administered at the doses of 1.0m/kg and 30mg/kg respectively. However, DOMP nanoparticles showed the anti-emetic effect at lower doses compared to that of control standard and unprocessed DOMP. Furthermore, there was observed a substantial % increase of antiemetic potential for DOMP nanoparticles compared to the unprocessed DOMP and the standard metoclopramide.