Cancer-related fatigue (CRF) is a prevalent and persistent symptom from androgen deprivation therapy (ADT) in prostate cancer. The Mediterranean-style dietary pattern (MED-diet) offers a plausible mechanism to mitigate CRF through reducing inflammation and improving body composition. This study aimed to evaluate the effects of a 12-week MED-diet, compared to usual care, on CRF and quality of life in men with prostate cancer treated with ADT. Twenty-three men (65.9 ± 7.8 years; body mass index: 29.6 ± 2.7 kg/m2; ADT duration: 33.8 ± 35.6 months) receiving ADT for ≥3 months were randomly assigned (1:1) to 12-weeks of usual care or the MED-diet involving six individualised nutrition consults. Primary outcomes included CRF Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale (FACIT-F) and quality of life FACIT-General (FACIT-G), secondary outcomes included body mass/composition and interleukin (IL)-6 and IL-8 concentrations measured at baseline, 8-weeks and 12 weeks. Intervention feasibility was measured by intervention safety, study completion rate, consult attendance, and adherence to the MED-diet through the Mediterranean-diet adherence screener (MEDAS). Intention to treat linear mixed models were used to determine changes in outcomes between the MED-diet and usual care at baseline, 8-weeks and 12-weeks. The MED-diet improved CRF (FACIT-F) at 8-weeks +4.8 (0.0, 9.8); P = 0.05 and 12-weeks +7.2 (2.2, 12.0); P = 0.005, quality of life (FACIT-G) at 12-weeks +9.2 (2.7, 15.8); P = 0.006, reduced total body mass at 8-weeks −2.51 kg (−4.25, −0.78); P = 0.005 and 12-weeks -2.97 kg (−4.71, −1.25); P = 0.001, lean mass at 8-weeks −1.50 kg (−2.91, −0.10); P = 0.036, and IL-8 at 8-weeks -0.18 ng/ml (−0.34, −0.02); P = 0.029 compared to usual care. The MED-diet demonstrated zero adverse events, 91% study completion, 100% attendance, and 81% adherence to the MEDAS. The MED-diet is safe and feasible, and has the potential to improve CRF and quality of life in overweight men treated with ADT compared to usual care. Further exploration of the MED-diet is warranted in a larger powered sample size to consolidate these findings.