Aim: We aimed to evaluate the psychological well-being and overall well-being in offspring and their parents following kidney transplantation, in comparison to a group of healthy individuals and offspring diagnosed having severe lymphoblastic leukemia. Furthermore, our goal was to discover potential issues related to compromised mental health and overall well-being by examining various health indicators. Methods: The study involved the examination of forty children who had undergone renal transplantation, having an average age of 12 years (ranging from 2 to 18 years). The evaluation of mental well-being involved the utilization of the Pediatric Quality of Life Inventory 5.1 Generic Core Scales and the Strength and Difficulties Questionnaire. The General Health Questionnaire and the Quality-of-Life Scale (QOLS) were employed to assess the mental well-being and quality of life of each mother. Results: The control group consisted of fifty children diagnosed with acute lymphoblastic leukemia, with a median age of 12 years (ranging from 7.6 to 16.5 years), and 43 healthy children, with the median age of 12 years (ranging from 9.7 to 16 years). Analysis of the study included treadmill exercise data from 23 out of 40 patients. Children who had undergone transplantation (referred to as TX children) exhibited noticeably elevated rates of mental health difficulties and reduced health-linked quality of life (HRQOL) during the time frame of 3 to 14 years post-transplantation when compared to both control groups. Body mass index and maximum oxygen uptake (evaluated in a subset of 23 out of 39 individuals) were discovered to have a substantial influence on the mental well-being of children (estimated by SDQ) and child quality of life (QOL). Conclusion: These findings lead us to propose that post-transplantation rehabilitation for TX children should emphasize physical activity and quality of life enhancement as crucial elements, in order to mitigate the interconnected physical and psychological burden experienced by kidney transplant recipients.