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Phone and Internet-based interventions can improve the management of depression in primary care, and interventions using these communication channels are increasingly used to improve behaviors such as diet and physical activity. Increased physical activity has been shown to improve depressive symptoms, but to date there are no reports of the effects of a phone and Internet diet and exercise intervention on symptoms of depression in patients seen in primary care. This study assessed depressive symptoms in 401 participants in a randomized control trial of a 12-month primary care, phone and Internet-based behavioral intervention for overweight women. A one-way analysis of variance examining the mean change in Center for Epidemiological Studies Depression (CESD) score from baseline to 12 months, controlling for age, education, marital status, and employment showed that those receiving the intervention significantly decreased their CESD scores (P=.03) more than those receiving standard care. Although the intervention did not target depressed individuals or present material relating to mood management, those with probable depression (27% of the whole sample) showed clinically important improvements—a mean five-point change on the CESD short form. Participants who engaged more readily with the intervention were more likely to reduce their depression scores. A 1-year primary care based phone and Internet diet and exercise intervention can improve depressive symptoms in overweight women. Given the promise of phone and Internet-based interventions to improve both depression and lifestyle-related behaviors, and given that such interventions could extend the reach of primary care to many individuals at relatively low cost, these results suggest the need for further research, including the effects of additional mood management components.