Wisdom has been defined as a constellation of mature personality characteristics and expertise in the fundamental pragmatics of life. In the past decades, researchers have dedicated to the issues of definition and measurement rather than the growth of wisdom. Therefore, it is necessary to explore the factors and their internal mechanism that influence wisdom. The researches on the relationship between wisdom and age suggest that wisdom does not increase automatically with age, certain internal and external factors are necessary for wisdom to grow with age. Many empirical studies have revealed that self-reflection is both an important component of wisdom and an important factor and the process to promote wisdom. Moreover, studies indicate that searching for meaning plays an important role in the growth of individual wisdom, and self-reflection may also influence wisdom through the mediating process of searching for meaning. At the same time, previous researches suggest that the effect of self-reflection on wisdom through the mediating process of searching for meaning may be moderated by life events. For individuals who experienced more life events, the mediating effect may be stronger. The present study constructed a moderated mediating model and aimed to explore the effect of self-reflection on wisdom and to investigate the mediating effect of searching for meaning on the relationship between self-reflection and wisdom as well as the moderated effect of life events on this mediating process. A total of 1019 college students (841 female and 178 male with the age of 20.48 ± 1.94 years) were recruited as participants in the study and completed self-reflection scale, brief wisdom screening scale, searching for meaning questionnaire and adolescent self-rating life events checklist. The results indicated that self-reflection positively predicted wisdom, which confirmed self-reflection was a critical determinant of wisdom. Searching for meaning partially mediated the relationship between self-reflection and wisdom, specifically, self-reflection not only directly influenced wisdom, but also indirectly influenced wisdom through searching for meaning. Life events moderated the mediating effect of searching for meaning on the relationship between self-reflection and wisdom, life events moderated the second path of the mediation, to be more specific, self-reflection significantly influenced the wisdom through the mediating role of searching for meaning for the individuals who experienced more life events, whereas the indirect effect of self-reflection through search for meaning on wisdom was not significant for the individuals who experienced fewer life events. Therefore, the effect of self-reflection on wisdom was a moderated mediating model, and the indirect effect was significant for the individuals who experienced more life events. In conclusion, the present study not only revealed how self-reflection influenced wisdom, but also demonstrated when the mediating effect was stronger. At the theoretical level, these findings provided a way of thinking about the developmental mechanism of wisdom. In terms of practical implications, these findings suggested that in the interventions of wisdom-fostering, especially for individuals who had experienced many kinds of difficulties and hardships, they should be encouraged to conduct exploratory self-reflection on the negative life experiences and do the effortful work to find life meaning in these difficult experiences, so as to promote the development of their wisdom rather than other negative effects.