Background <p>The long-term management of chronic kidney disease (CKD) in adolescents places a heavy burden on their families; it also adversely affects adolescents’ quality of life (QoL). Family management adjustment and healthcare transition (HCT) readiness have been identified as important protective factors for quality of life among adolescents. This study aimed to explore the association between family management adjustment and QoL in adolescents with CKD and verify the mediating effect of HCT readiness in this relationship.</p> Methods <p>A total of 354 adolescents with CKD aged 10–18&#xa0;years (mean age 12.62; 52.8% male) and their parents were recruited. Participants completed the Family Management Measure, STARx Questionnaire, and PedsQL™ 4.0. Bivariate correlations, multiple linear regressions, and mediation analysis were the statistical analyses performed.</p> Results <p>The results revealed a significant indirect effect of family management adjustment on QoL via HCT readiness (<i>β</i> = 0.209, 95% CI [0.133–0.296]). The direct effect of family management adjustment on QoL remained significant after accounting for the mediator (<i>β</i> = 0.265, <i>p</i> &lt; 0.001, 95% CI [0.140–0.390]), indicating a partial mediation effect of HCT readiness.</p> Conclusions <p>This study shows that better family management adjustment is associated with better QoL in adolescents with CKD both directly and indirectly through its association with HCT readiness. These findings highlight the importance of supporting family management adjustment and fostering HCT readiness in clinical practice to optimize QoL in this vulnerable population.</p> Graphical abstract <p></p>