Population aging represents a global challenge. In this context, loneliness has positioned itself as a critical problem with adverse effects on the physical and mental health of the elderly. This study aimed to explore the role of negative self-perception of aging (SPA) and social isolation as mediators in the relationship between ageism and loneliness. Structural equation modeling (SEM) was used in a sample of 307 people over 50 in Chile. The results show that both age discrimination and ageist stereotypes are directly associated with higher levels of loneliness. Negative SPA significantly mediated the relationships between discrimination and loneliness, as well as between stereotypes and loneliness. These findings highlight the importance of psychological and cultural variables in objective and subjective outcomes of interpersonal relationships, suggesting the need for interventions to mitigate the effects of ageism and improve SPA to favor healthy aging.