The incorporation of lubricating filler can improve the self-lubricating properties of polymers and mitigate friction-induced vibration under harsh conditions. However, filler performances significantly vary depending on its size. In this study, molybdenum bisulfide (MoS2) particles of various sizes were utilized as lubricating additives to reinforce thermoplastic polyurethane (TPU). The results showed that an appropriate decrease in the particle size of MoS2 facilitated more efficient stress transfer from the polymer to the particle due to strengthened interfacial interaction, resulting in improved mechanical properties of the reinforced TPU composites. Additionally, the adsorption property of the MoS2 particle improved, extending the duration of the MoS2 tribo-film. These beneficial phenomena endow TPU composites with excellent tribological and frictional vibration reduction properties, with the 500 nm MoS2 presenting the best reinforcing effect. However, further reduction in particle size caused particle agglomeration, which adversely affected the mechanical and self-lubricating properties of the composite and eventually reduced the frictional vibration reduction properties. The findings obtained herein provide a valuable reference for developing a novel polymer with excellent friction and vibration reduction properties.