Objectives: The COVID-19 pandemic caused people to suffer from secondary problems such as social isolation and loneliness as well as experiencing anxiety about catching and spreading the virus. Existing research emphasizes the roles of cognitive flexibility and hope for psychological adjustment but the mediating and moderating mechanisms have not yet been researched widely. Therefore, this study examined whether hope mediated the relationship between loneliness and psychological adjustment problems and whether cognitive flexibility moderated this mediation effect of hope in the relationship between loneliness and psychological adjustment problems during the COVID-19 pandemic curfew in Turkey. Methods: A total of 512 Turkish students and young adults completed UCLA Loneliness Scale, Brief Psychological Adjustment Scale, Dispositional Hope Scale, and Cognitive Flexibility Inventory for this cross-sectional study. Results: The results indicated that loneliness had a significant and positive predictive effect on the psychological adjustment problems and that this relationship was partially mediated by hope. Further, psychological flexibility moderated the relationship between loneliness and hope. Conclusions: The current study contributes a better understanding of the influence of loneliness on psychological adjustment, especially during the COVID-19 curfew period.