There is substantial evidence supporting that improving diet quality leads to improved health-related quality of life (HRQoL). Our major aim was to assess the effectiveness of a Mediterranean diet–based nutritional intervention to improve HRQoL in the context of a secondary prevention trial of depression. Secondarily to assess its effectiveness among adults aged 60 or more years. The PREDIDEP study is a 2-year multicentre, randomized, single-blinded nutritional trial. At baseline and at 1-year and 2-year follow-up, SF-36 health survey questionnaire was collected to evaluate participants' HRQoL (total and specific range for each of the 8 dimensions: 0 to 100 points). Mixed effect linear models were used to assess changes in HRQoL according to adherence to the Mediterranean diet. The trial was registered at ClinicalTrials.govNCT03081065. After 2 years of intervention, the Mediterranean Diet intervention group compared to control group (without nutritional intervention, only usual clinical care) showed an improvement in some dimensions of HRQoL such as Mental Health (7.22; 95 % CI = 2.22–12.22) (between-group difference: 6.79; 95 % CI −0.14–13.73, p = 0.055); Vitality (9.51; 95 % CI = 4.00–15.03) (between-group difference: 9.00; 95 % CI 1.75–16.25, p = 0.020); Mental Summary Component (2.83; 95 % CI = 0.55–5.11) (between-group difference: 1.17; 95 % CI = −1.96–4.30, p = 0.462); and General Health (10.70; 95 % CI = 5.58–15.81) (between-group difference: 6.20; 95 % CI = −0.89–13.28, p = 0.086). Similar results were observed for participants aged 60 or more years. The intervention based on Mediterranean diet in patients with previous depression seems to be effective in improving HRQoL, especially the mental dimensions. This effect is also observed among participants aged 60 or more years. •A Mediterranean diet intervention is effective to improve quality of life of patients with previous depression•A Mediterranean diet intervention in patients recovered from depression improves particularly their mental quality of life•A Mediterranean diet intervention increases the quality of life of patients aged 60 or more years with previous depression