Background and Objectives: Pain or nociception is a devastating experience that alters both the physiological and psychological status of individuals. A variety of chemical and physiological tissue damage and physical parameters like temperature, pressure, etc. induce pain. Clinically, pain is managed through the administration of antinociceptive drugs. In the current work, the antinociceptive potential of Mentha piperita leaves against pain in the zebrafish model has been explored. Materials and Methods: Formalin was injected in the tail of the zebrafish to induce pain and was exposed to 5, 10, 15, and 20 mg of the extract. The behavioral pattern was analyzed using the Behavioral Observation Research Interactive Software (BORIS). Gene expression and enzymatic studies were performed to evaluate inflammation, oxidative stress and the antioxidant ability of M. piperita. Results: In the open field test, animals treated with the leaf extract restored their activity to normal in a dose-dependent manner. Pain-induced animals inclined toward darkness, whereas the treated animal preferred to stay in the light. Furthermore, behaviors such as freezing, inaction, and altered swimming patterns were all restored to normal conditions. The color change in the tail was prominent in pain-induced animals, whereas it was restored to normal in the treated group. The higher dose of the plant extract was effective in downregulating the expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-α), thereby impairing the neuroinflammation. The plant extracts reduced reactive oxygen species (ROS) and nitric oxide levels, whereas it increased reduced glutathione levels. Conclusion: The current work establishes that Mentha piperita is effective in ameliorating pain in a zebrafish model.