Peer victimization is prevalent among college-aged students, yet no study to our knowledge has examined various strategies of defending peers from victimization among this population. This study investigated the associations between multiple defending strategies (i.e., direct, indirect, including prosocial and aggressive defending), how moral disengagement and perception of harm were associated with multiple defending strategies, and gender differences in these associations. Participants were 372 ethnically diverse college students (18–53 years old, M = 21.24, SD = 4.13; 76% women) from a medium-sized university who watched two short videos depicting events of peer victimization and answered questions about how they would respond. Structural equation modeling was used to examine the associations between key variables, and multi-group modeling was used to assess gender differences in defending responses predicted by moral disengagement and perception of harm. Results showed that college students used both prosocial and aggressive defending strategies. Moral disengagement and perception of harm were associated in generally expected ways with defending strategies, but the associations differed across victimization scenarios and participant gender. Interventions to encourage college students to defend should stress the use of prosocial rather than aggressive strategies and be tailored to differences in defending responses based on form of victimization.