Introduction: The enzyme cyclooxygenase (COX) has been implicated to be a key enzyme involved in recruiting inflammations. Developing COX inhibitors has remained one of the important aspects of developing novel and safe anti-inflammatory agents. An attempt has made to find the medicinal plants as alternatives to presently available NSAIDs (Non steroidal anti-inflammatory drugs). Methods: In the present study the samples of Enicostema axillare (Lam.) Raynal. [Gentianaceae], Argemone mexicana L. [Papaveraceae], Clerodendrum multiflorum (Burm.f.) O. Ktze. [Verbenaceae], Withania somnifera (L.) Dunal. [Solanaceae], Polyalthia longifolia (Sonner.) Thw. [Annonaceae] and Vitex nigundo L. [Verbenaceae] were sequentially extracted in water, ethanol and hexane and were evaluated in-vitro for COX-1 and 2 inhibitory activities. The free radical scavenging activities were carried out along with cytotoxicity evaluation. Results: Among the tested plants, E. axillare showed promising COX-2 inhibiting activity in ethanol (48.71 ± 0.035 %), water (42.13 ± 0.030 %) and hexane (12.31 ± 0.040 %) as compared to COX-1 inhibition in ethanol (14.73 ± 0.030 %), water (27.64 ± 0.030 %) and hexane (6.92 ± 0.031 %). The contents of the water extracts of majority of the plant samples were found to interact with DPPH, superoxide and OH radicals. The selected plants did not showed cytoxicity except a poor toxicity demonstrated by ethanol extract of P. longifolia (0.15 ± 0.040 %). HPTLC analysis was carried out to study the flavonoids diversity of the selected plant samples. Conclusion: The results obtained shows that majority of the plants under study were found to inhibit COX-2 activity significantly as compared to COX-1 activity. However, more detailed studies are required to assess the safety and efficacy of these plants.