The handloom weaving industry is integral to developing countries, especially in South Asia, where traditional techniques are still widely practiced. In India, the handloom sector is a significant part of the informal economy, employing millions and preserving rich cultural heritage. Despite its economic and cultural importance, the sector faces severe challenges, including poor working conditions that lead to a high prevalence of work-related musculoskeletal disorders (WMSDs). This study focuses on assessing the prevalence of musculoskeletal morbidity and the effectiveness of physiotherapy interventions in reducing WMSDs among handloom weavers in Kanchipuram, Tamil Nadu. This quasi-experimental study utilized a pre- and post-test design conducted over 12 months. A total of 121 handloom weavers from four major cooperative societies in Kanchipuram were selected using multistage sampling. Inclusion criteria were adults over 18 years, full-time weavers with more than a year of experience, and those who consented to participate. The study involved initial data collection through interviews using a pre-tested semi-structured questionnaire and the Standardized Nordic Musculoskeletal Questionnaire to assess pain prevalence. The intervention phase included physiotherapy exercise training thrice a week for three months, followed by post-intervention data collection and analysis. Pre-intervention data indicated high prevalence rates of musculoskeletal pain, with 62% of participants reporting knee pain and 54.5% reporting ankle/foot pain over the past year. Post-intervention assessments showed significant reductions in pain across all body parts, with the most substantial decreases in knee and shoulder pain. For instance, knee pain scores decreased from 3.10 ± 2.61 to 1.81 ± 1.69. The overall mean pain rating significantly dropped from 1.72 ± 0.88 pre-intervention to 1.00 ± 0.50 post-intervention, demonstrating the effectiveness of the physiotherapy exercises. The study confirms the high prevalence of musculoskeletal disorders (MSDs) among handloom weavers and demonstrates the significant impact of physiotherapy interventions in alleviating pain. Implementing regular physiotherapy exercises can substantially improve the well-being and productivity of handloom weavers, ensuring the sustainability of this vital cultural and economic industry. The results advocate for policy changes and increased support for ergonomic and health interventions in the handloom sector.