Robust evidence for interventions to improve health-related quality of life (HRQoL) in people who receive a kidney transplant is scarce. We aimed to assess the effects of a lifestyle intervention in this context. We conducted a multicentre, open-label, parallel-group, randomised controlled trial among people who have received a kidney transplant. Participants from six hospitals across the Netherlands were randomly assigned 1:1:1 by an independent company into: usual care, exercise, and exercise plus diet. The exercise intervention encompassed two phases, a 3-month supervised exercise programme (twice weekly) followed by 12months of lifestyle coaching, with 15months of additional dietary counselling (12 sessions) for the exercise plus diet group. The primary outcome was HRQoL-domain physical functioning, assessed using the 36-item Short Form Survey at 15months. From Oct 12, 2010to Nov 18, 2016, 221participants who had received a kidney transplant (138 [62%] male and 83 [38%] female, with a mean age of 52·5 [SD 13·5] years, who were a median of 5·5 [IQR 3·6-8·4] months post-transplant) were included and randomly assigned to usual care (n=74), exercise intervention (n=77), and exercise plus diet intervention (n=70). In the intention-to-treat analyses, at 15months post-baseline, no significant differences inHRQoL-domain physical functioning were found for the exercise group (5·3arbitrary units, 95% CI -4·2to 14·9; p=0·27), and the exercise plus diet group (5·9arbitrary units, -4·1to 16·0; p=0·25) compared with control. Safety outcomes showed no safety concerns. After 3months of supervised exercise intervention, HRQoL-domain physical functioning improved in the exercise group (7·3arbitrary units, 95% CI 1·2to 13·3; p=0·018) but not in the exercise plus diet group (5·8arbitrary units, -0·5to 12·1; p=0·072). A lifestyle intervention is safe and feasible in people who have received kidney transplants, paving the way for lifestyle intervention studies in other multimorbid populations with polypharmacy. However, improving HRQoL for people who have received a kidney transplant is challenging. The lifestyle interventions in the current study did not show significant improvements in HRQoL at the end of the study at the total group level. Dutch Kidney Foundation, Innovation Fund of the Dutch Medical Insurance Companies, and University Medical Center Groningen.