Objective: Pilot study to assess the efficacy of a multidisciplinary educational training program (OverdosED) designed to increase college students' knowledge of and confidence in their ability to appropriately recognize and respond to suspected overdose on depressant substances. Participants: Undergraduate students (n = 92) with Greek life affiliations at a moderately-sized private liberal arts college in the southeastern USA. Methods: Electronic surveys were administered before and after delivery of the training program. Questions assessing knowledge of depressant substance overdose were compared to determine the impact of the educational intervention. Questions assessing participants' confidence in their ability to recognize and respond to overdose and their perceptions of campus culture were also compared. Results: Mean composite scores on knowledge-based questions were significantly higher for the post-intervention survey compared to the pre-intervention survey. Confidence in knowledge also significantly increased after the intervention. Mean scores for survey responses related to campus culture were high at baseline but significantly increased after the intervention. Conclusions: OverdosED successfully increased college students' knowledge of and confidence in their ability to appropriately recognize and respond to suspected overdose on depressant substances, and positively influenced perceptions on campus culture.