Cyberbystanders play a significant role in stopping cyberbullying. The aim of this review was to identify and quantify the factors contributing to the defending behavior of adolescent cyberbystanders. A systematic search of PsycARTICLES, PubMed, PsycINFO, MEDLINE, and Scopus databases, manual searches, and citation tracking were conducted in line with PRISMA guidelines. Meta-analyses were performed for the selected factors. Peer-reviewed journal articles that evaluated adolescent cyberbystanders' defending behavior as an outcome or dependent variable were included. For each study, we estimated the risk of bias, the level of evidence, and the degree of association with defending behavior. Both the systematic review and the meta-analysis indicated positive associations of empathic skills and cyberbullying victimization with the defending behavior of adolescent cyberbystanders. Moreover, the systematic review showed that also self-efficacy and reinforcing the bully were related to defending behavior. The results of our review highlight the importance of being able to empathize with the victim's experiences as a factor contributing to the defending behavior of adolescent cyberbystanders. In subsequent research, it is worth differentiating between constructive and aggressive forms of defending behavior and using reliable research tools. Preventive and psychoeducational programs for adolescents should be focused on teaching specific and clearly described constructive defending behaviors in situations of cyberbullying.