This study investigates the relationship between self-esteem and psychological well-being among students with mobility disabilities, focusing on the mediating roles of grit and optimism. Grounded in positive psychology, the research adopts a cross-sectional quantitative design involving a sample of university students with disabilities. The present study employed the serial mediation model to examine the serial mediation effects of grit and optimism in the relationship between self-esteem and psychological well-being. 203 participants with mobility disability were selected using a purposive sampling technique from various institutions of Uttar Pradesh. Standardized measures were used to assess self-esteem, grit, optimism, and psychological well-being. The findings indicate a significant positive association between self-esteem and psychological well-being. Moreover, grit and optimism were found to partially mediate this relationship, suggesting that higher self-esteem contributes to greater psychological well-being through enhanced grit and a more hopeful outlook. These results underscore the importance of fostering self-esteem and cultivating personal strengths like grit and optimism to promote mental health and well-being in students with physical disabilities. Implications for educational policies and support programs aimed at inclusive psychological development are discussed.