Rheumatoid arthritis (RA) is an immunocompromised disorder characterized by a marked increase in the synthesis of inflammatory molecules that stimulates the destruction of bones and cartilage. The conventional treatment modalities for RA are associated with adverse side effects and lack sensitivity, suggesting an immediate demand for alternate beneficial therapeutic remedies. The current study sought to understand more about zerumbone's anti-inflammatory properties in diagnosing collagen-induced arthritis (CIA) in experimental animals. The current study observed that zerumbone reduced clinical severity in CIA-induced animals compared to healthy animals. Zerumbone administration significantly decreased (p < 0.001) the concentration of SOD, CAT, GR, and GSH in treatment groups. Zerumbone administration drove down significantly (p < 0.001) the concentration of inflammatory cytokine molecules. Zerumbone was effective in bringing significant changes in levels of MPO, NO, LDH, MMP-8, and ELA. The therapeutic potential of zerumbone was found to be associated with reduced joint destruction and restored normal histology in the cartilage and tissue. Adsorption, distribution, metabolism, excretion, and toxicity studies were used to determine the druglike properties of zerumbone. ProTox-II studies revealed that zerumbone did not possess toxic properties like hepatotoxicity, immunotoxicity, carcinogenicity, mutagenicity, and cytotoxicity. Therefore, the present study evaluated the therapeutic properties of zerumbone in CIA animal models.