This study was based on evaluating anti-inflammatory activities of ethanolic extracts from Stevia leaves (EESL) and Fenugreek seeds (EEFS) (in vitro and in vivo). In the in vitro experiment, the results exhibited potent anti-inflammatory activity. The combination of both extracts (1:1, 100 g) showed to be the most potent inhibitor of COX-2 with inhibition % (83.64%). This result was comparable with the standard Celecoxib showed higher level of inhibition, (86.63%, 100 g). While, EESL showed the highest activity as COX-1 inhibitory activity (74.35%, 100 g), which it is higher than standard Celecoxib (67.64%, 100 g). In vivo anti-inflammatory activity was performed on Wistar rats at the doses 200 and 400 mg/kg body weight using the carrageenan-induced rat paw edema modal. Combination of (SLEE + FSEE, each 100 mg) displayed the highest significant anti-inflammatory activity (0.46ef± 0.025, p < 0.05) after 4 h, compared with indomethacin (0.44f ± 0.025, p < 0.05). The results indicated that these plants may have a role for discovering new anti-inflammatory natural drugs. Furthermore, Stevia leaves and Fenugreek seeds can be subjected to further investigations as anticancer agents.