While most players enjoy video gaming, a minority suffer from problematic gaming. Existing studies focused on risk factors and proposed legislative and technological measures to contain the undesirable consequences. The present study aims to examine whether players’ healthy gaming practices can protect themselves against problematic gaming. We conducted a longitudinal survey at a public university in China, 604 college students took the first wave survey, and 365 of them completed the second wave six months later. The results showed that protective gaming beliefs and behaviors at baseline were negatively associated with problematic gaming tendency, and positively associated with mental health and well-being at follow-up. Problematic gaming tendency did not predict mental health and well-being. The findings suggested that players’ self-regulation can be an effective measure against problematic gaming and promote mental health and well-being. The present study can inspire stakeholders to develop additional approaches to help at-risk and problematic players.