BackgroundCancer diagnosis not only impacts physical health but also mental well-being, often leading to significant stress, fear, and depression among patients.The utilization of CAM has shown a rising trend, influenced by the availability of different modalities offered by healthcare services, sometimes in an ad hoc fashion. This study seeks to examine and compare the respective impacts of warm foot baths and foot reflexology on depression in patients undergoing radiotherapy. MethodsA randomized clinical trial was conducted at Mashhad University of Medical Sciences in Iran in 2019, following CONSORT guidelines. Participants included non-metastatic cancer patients aged 18–60 undergoing a 28-day radiotherapy course. Patients were randomly assigned to receive either warm footbaths or foot reflexology as interventions, performed daily for 20 min over 21 days. The data were analyzed using appropriate statistical tests. ResultsStatistical analysis indicated no significant differences in demographic attributes between the two groups. Both interventions led to a significant reduction in depression scores post-treatment compared to pre-treatment assessments. Foot reflexology showed a greater reduction in depression scores compared to footbaths with warm water. ConclusionsBoth warm footbaths and foot reflexology are effective in alleviating depression in patients undergoing radiotherapy, with foot reflexology showing a greater impact on improving depression levels. The study recommends foot reflexology as a preferred intervention for managing depression in these patients if conditions and facilities permit.