Curcumin, the active ingredient of the spice turmeric, has been shown to have anticancer activities in several preclinical and clinical studies. The prophylactic effect of curcumin against chemotherapy-induced damage and side effects was evaluated in a double-blind, placebo-controlled randomized trial. Eighty cancer patients on standard chemotherapy regimens were randomly assigned to receive curcumin as adjuvant therapy (500 mg per 12 hours) and matched control group to receive placebo for 9 weeks. Pre- and post-intervention, the changes in the health-related quality-of-Life (QoL) score (based on the University of Washington Quality-of-Life (UW-QoL) questionnaire, version 3), clinical symptoms, and hematological and biochemical parameters were assessed. Comparison between groups based on total QoL score showed that curcumin supplementation was not associated with improved QoL (P = 0.102). Hematological and biochemical analysis showed no statistical differences between the groups at the end of the trial (P > 0.05). However, during the trial, significant differences were observed in hemoglobin (Hb), hematocrit (HCT), lactic acid dehydrogenase (LDH), serum glutamic-oxaloacetic transaminase (SGOT), and anaplastic lymphoma kinase (ALK) between the groups (P < 0.05). Future studies in a larger homogenous population of cancer patients are required to confirm the adjuvant effect of curcumin on chemotherapy-induced QoL.