Complementary Alternative Medicine (CAM) has been widely used in the world, but limited data are available on the use of CAM in depression. This study aimed to evaluate the use of CAM and its associated factors in depression. This cross-sectional study was conducted on 300 depressed patients referred to the Yasuj Neurology and Psychiatric Clinic, southern Iran, between 2019 and 2020. A valid semistructured international questionnaire was used; amongst the participants, 230 (77%) were female. The mean age of the patients was 41.47 ± 12.2 years and the mean duration of the disease was 4.49 ± 4.88 years. The prevalence of CAM use was 37.6% among the patients. The results showed a significant difference between the CAM users and nonusers regarding the disease duration (=0.045) and body mass index (=0.007). Moreover, the results of logistic regression analysis revealed a significant relationship between CAM use and female gender, disease duration, overweight, obesity, and self-employment (=0.039, =0.028, =0.029, =0.048, and =0.044, resp.). The most frequently used type of CAM was herbal medicine (97.35%) followed by pray therapy (23.89%). Additionally, the most widely used herbs were borage (77%), chamomile (46.9%), and lavender (21.2%). Furthermore, 62.8% of the patients reported that their main reason for using CAM was its effectiveness. The majority of the patients (77%) had not consulted their physicians prior to utilization of CAM therapies. Herbal medicine was the most common form of CAM in depression, with a high satisfaction level. Thus, it is necessary to increase physicians' awareness in different fields of CAM.