Background <p>The population of older adults with disabilities in China is increasing rapidly, imposing substantial caregiving pressures on their families. However, the relationship between loneliness and perceived stress among these caregivers, as well as the potential mediating role of psychological resilience, remains insufficiently explored.</p> Methods <p>A convenience sampling method was used to conduct a questionnaire survey of 311 family caregivers of older adults with disabilities at a tertiary hospital in Guangzhou, China. The Barthel Index, the Chinese Perceived Stress Scale (CPSS), the UCLA Loneliness Scale-6 (ULS-6), and the Connor–Davidson Resilience Scale (CD-RISC) were used to measure variables. The mediating role was analyzed via structural equation modeling.</p> Results <p>After controlling for key covariates, structural equation modeling supported a partial mediation model. Loneliness influenced perceived stress both directly (β = 0.503) and indirectly via psychological resilience (β = 0.245, 95% CI [0.152, 0.394]), with the mediation accounting for 32.8% of the total effect.</p> Conclusion <p>The findings underscore the mediating role of psychological resilience in the link between loneliness and perceived stress, suggesting that it may be a valuable target for future interventions aimed at mitigating the psychological burden of caregiving.</p> Clinical trial number <p>Not applicable.</p>