Background: The prevalence of polypharmacy and hyperpolypharmacy in India is a growing concern, particularly among the elderly. With over 49% of the elderly population engaged in polypharmacy and 31% in hyperpolypharmacy, the resultant issues of potentially inappropriate medications (PIMs) are increasingly evident. These medications, often unnecessary, can lead to severe adverse effects, diminishing the quality of life for a significant portion of this demographic. Addressing these issues is imperative for enhancing healthcare outcomes and necessitates the development of deprescribing guidelines that cater specifically to the Indian healthcare context. Objective: This opinion aims to provide a structured approach to deprescribing, targeting the minimization of risks associated with unnecessary medication use among the elderly in India. The primary goal is to establish evidence-based, practical guidelines adaptable to diverse healthcare settings across the country, ensuring both safety and efficacy in medication management. Methods: The development of this opinion involved a comprehensive interdisciplinary approach, incorporating inputs from clinical pharmacologists, geriatricians, internal medicine experts, endocrinologists, gastroenterologists, cardiologists, primary care physicians, pharmacists, and patient advocacy groups. An expert panel was formed to conduct extensive literature reviews, ensuring a robust evidence base for the opinion development. Consensus meetings were held to harmonize expert opinions and integrate clinical practices with empirical evidence. Pilot testing in various healthcare settings, both urban and rural, was crucial for evaluating the practicality and effectiveness of the guidelines. Feedback from these tests was used to refine the guidelines further, ensuring their relevance and applicability across different regions and healthcare systems within India. Results: The opinion outlines a systematic approach to deprescribing, including the identification of PIMs through validated tools like the Beers and STOPP/START criteria. They emphasize the importance of assessing individual patient risks, such as drug-drug and drug-disease interactions, before initiating any changes to medication regimens. A key component is the implementation of a patient-centered care model, emphasizing shared decision-making between healthcare providers and patients. This approach is expected to foster better patient engagement and compliance. The anticipated impact of these guidelines includes a reduction in adverse drug events, increased medication adherence, and overall improvement in the health and well-being of the elderly population. Conclusion: The opinions presented are poised to transform prescribing practices across India by reducing unnecessary medication use among the elderly. By focusing on evidence-based interventions, patient-specific considerations, and collaborative care approaches, these guidelines are expected to mitigate the risks associated with polypharmacy and enhance the quality of life for older adults. The successful implementation of these guidelines requires ongoing education and support for healthcare providers, as well as regular updates based on emerging evidence and clinical outcomes.