Pain is a challenging issue to be addressed in osteoarthritic (OA) patients, and the current drug therapy could only handle mild to moderate pain. The optimal medication for treating osteoarthritis would be that, which can reduce pain, alleviate symptoms, have minimal side effects, and do not interact with other medications. Capsaicin, an aromatic compound found in cayenne pepper, is being investigated and found to be effective in treating and managing specific peripheral pains. Capsaicin desensitizes neurons in two ways: first, through reversible capsaicin-induced loss of reactivity, and second, via calcium-induced desensitization through phosphatase activation and subsequent inactivation of capsaicin channels. Capsaicin selectively activates TRPV1 (Transient Receptor Potential Vanilloid 1), a Ca2 + -permeable cation channel found at many nociceptor terminals. Upon the completion of this pathway, there is a decrease in the response to unpleasant stimuli. Most capsaicin-sensitive nociceptors are known to respond to various sensory stimuli, including stress, heat, and biochemical stimuli. Substance P which is released by nociceptors, and is involved in the pathophysiology of osteoarthritis and is responsible for causing pain in the joints. It is raised in plasma and synovial tissue in individuals with osteoarthritis and is also believed to contribute to cartilage degradation. The present manuscript discusses the molecular mechanisms of OA and the therapeutic mechanisms of capsaicin to understand its role in treating OA. Besides these, it also discusses the effect of Capsaicin on other body tissues such as the central nervous system and cardiac tissue.