Severe self-loosening behavior, accompanied by the friction and wear at the threads, will be caused under cyclic transverse loads, resulting in degradation or even failure of the structure. In this work, an experimental study on the loss of bolt preload under cyclic transverse loads was carried out. The results of cyclic transverse loading tests showed that when the bolt preload does not exceed a certain threshold, the increased bolt preload can improve the anti-loosening performance of bolted joint. Subsequently, the finite element analysis model of bolted joint with the thread lead angle considered is developed by means of parametric modeling to investigate the evolution of stress state at threads under cyclic transverse loads. Finite element analysis results showed that after the completion of tightening, the stress distribution of the first layer is the largest, followed by a decreasing form. As the number of cyclic loads increased, the degree of uneven stress distribution in the threads decreased. Once the threshold was exceeded, further increase in the bolt preload will reduce the ability to improve the anti-loosening performance. Through the observations of the surface morphology at threads, it showed that the most significant friction and wear was observed at the first layer thread, which is consistent with the result of finite element analysis.