Background: For the first time, the anti-inflammatory drugs: celecoxib, aspirin DL-lysine, niflumic acid, naproxen sodium, ibuprofen, and betamethasone are investigated for their inhibition activity against lipase. Objective: This work aims to demonstrate the inhibitory effect in vitro & in silico of six anti-inflammatory drugs on the enzymatic activity of two lipases. Method: In vitro study using p-nitrophenyllaurate as lipase substrate is used to determine inhibition potency. Molecular Docking is performed using the Autodock Vina for six drug molecules and two enzymes Candida rugosa lipase and human pancreatic lipase. Results: Bethametasone is the only one that represents an important inhibition effect with a value of IC50 of 0.36±0.01 mg/ml; while the other drugs represent values of IC50 > 2 mg/ml, signifying a very low inhibitory effect. Molecular docking allowed us to understand inhibitory – enzyme interactions and to confirm in vitro obtained results. Conclusion: These experiments showed that betamethasone can be used in the treatment of obesity and other diseases related to lipase activity.