This study is focused on the synthesis and exploration of Schiff’s base imidazole derivatives with the aim of assessing their anti-inflammatory activity. A series of compounds were synthesized and characterized using spectroscopic techniques. In-silico docking analysis was employed to identify potential active ingredients. The anti-inflammatory properties of these derivatives were then investigated using paw edema model induced by carrageenan followed by assessment of TNF-α and IL-1β as inflammatory cytokines. Results showed that specific Schiff’s base Imidazole derivatives, notably C1IN, C2IN, C4IN, C5IN, and C11IN, demonstrate significant effectiveness in alleviating paw edema and reducing the level of IL-1β and TNF-α. The findings emphasize the potential of these developed derivatives as viable options for anti-inflammatory intervention. The observed reduction in paw edema and cytokine levels signifies a promising anti-inflammatory profile, positioning these compounds as candidates for further exploration and development. The study contributes valuable insights into the anti-inflammatory properties of imidazole derivatives, suggesting their potential therapeutic applications in inflammatory conditions. Future research should delve deeper into mechanistic aspects and conduct additional preclinical studies to validate the translational potential of these derivatives in anti-inflammatory pharmacotherapy. This research opens avenues for the development of novel anti-inflammatory agents with potential clinical relevance.