Objectives Research has shown the role of mindfulness and self-compassion in promoting resilience while living with a disabling condition. However, little is known on the influence of these variables on sexual and relationship satisfaction of people with physical disabilities. This cross-sectional study aimed to explore the contribution of mindfulness, self-compassion, and acceptance in predicting sexual and relationship satisfaction, above and beyond experiencing physical disability. Methods A sample of 377 participants, aged between 18 and 55 years old, took part in a survey. Of these, 189 participants had a self-reported physical disability, the majority (70.1%) being either motor or neuromuscular health conditions. Results Findings showed that higher levels of mindfulness, self-compassion, and acceptance significantly predicted higher sexual (ΔR 2 = between .081 and .166; p < .05) and relationship satisfaction (ΔR 2 = between .072 and .106; p < .05), above and beyond the physical condition of the participants. Additionally, the physical condition was a moderator for the relationship between the mindfulness dimension of self-compassion and sexual satisfaction (ΔR 2 = .024; p = .037), as this association was only significant for people with physical disabilities. Conclusions This study explores possible vulnerability and protective psychological mechanisms that may be involved in sexual and relationship satisfaction, above and beyond the effects of the physical disability. Despite its limitations, findings call into attention for the importance of further research on mindfulness-related variables in optimizing sexual health in people with and without physical disabilities.