Parental burnout is overwhelming exhaustion associated with one’s parental role. Numerous studies have explored the antecedents of parental burnout, with a deficient focus on its consequences, especially for children’s development. This study investigated the interaction effect between two protective factors (i.e., co-parenting and parental psychological flexibility) of parental burnout on subsequent children’s mental health through the mediation effect of parental burnout. A total of 262 Chinese mothers (Mage = 35 years old) raising preschoolers participated in a two-wave survey within 1-month interval. Path analysis confirmed the moderated median model. Specifically, parental psychological flexibility (PPF) moderated the mediating effect of parental burnout between co-parenting and children’s internalizing and externalizing problems reported by mothers. For mothers with middle or low PPF, high-quality co-parenting was related to low children’s externalizing and internalizing problems via low-level parental burnout. While mothers with high PPF were less likely to develop parental burnout and exert a negative impact on children’s externalizing and internalizing problems even in face of low-quality co-parenting. Co-parenting and PPF may compensate for each other as the protective factors of parental burnout in mothers and children’s internalizing and externalizing problems in China.