<p>Porcine epidemic diarrhea virus (PEDV) is the primary pathogen responsible for highly contagious intestinal infections in pigs, which results in significant economic losses to the global animal husbandry industry. PEDV is an enveloped virus that enters cells via endocytosis, a process that is dependent on the binding of the viral surface S protein to a receptor on the host cell membrane. This results in a series of biomechanical alterations that drive the fusion of the viral and host cell membranes. These alterations stabilise the binding of the virus to the receptor and also affect the tension and the curvature of the plasma membrane and the formation of endocytic vesicles. A comprehensive understanding of the mechanism by which PEDV enters cells and the biomechanical changes that accompany this process is of paramount importance for the development of PEDV inhibitors, vaccines, and disease prevention and control strategies. Here, we review the general mechanism of PEDV entry, the biomechanical phenomena that occur during endocytosis, and the potential applications of biomechanics in antiviral therapy. It is anticipated that by gaining insight into these mechanisms, novel approaches to regulating viral entry pathways through mechanical interference, vaccine development, and antiviral drug design can be explored.</p>