Abstract Objective This study was designed to investigate the efficacy and feasibility of a web-based depression stigma education tool for healthcare professionals. Methods A web-based depression stigma program utilizing adult learning theories was developed. Forty-two consecutive subjects were enrolled from University of Maryland staff and graduate students. Primary outcomes were Bogardus Social Distance Scale with a vignette on major depression disorder (BSDS-MDD) and the Depression Stigma Scale (DSS) administered before and after the intervention. Results Internet-based education significantly decreased the level of depression stigma (BSDS-MDD 10.6 ± 4.4 versus 7.2 ± 4.4, p < 0.001; DSS-personal 12.7 ± 7.2 versus 7.8 ± 5.3, p < 0.001; DSS-perceived 21.7 ± 5.5 versus 12.4 ± 5.5, p < 0.001). After the educational intervention the subjects’ knowledge about depression significantly improved (pre-test DKS = 18.2 ± 8.2 versus post-test DKS = 20.6 ± 4.1, p < 0.001). The program was very well accepted by participants. For 100% of participants, it was not difficult to operate the program. Conclusions Computer-assisted education was effective in reducing the stigma of depression and increasing knowledge about depressive disorder. A web-based intervention has the potential to be used for educating graduate students and university staff about depression and for reducing depression stigmata. Healthcare professionals interacting with people with stigmatizing conditions can benefit from web-based computer education.