Osteoarthritis is one of the most common joint diseases, leading to joint pain, dysfunction, and a reduced quality of life for patients. Therefore, it is particularly important to explore more effective prevention, treatment and management methods to relieve patients’ pain and enhance their quality of life. Among physical therapies, pulsed electrical stimulation (PES) is considered to be a promising treatment method due to its high safety and ease-of-use features. PES provides a non-invasive, safe and effective option for patients. However, there are fewer studies on the biomechanical changes of PES in periarticular tissues, and its effects on the biological behavior of chondrocytes remain unknown. This study investigated the effects of PES on the biomechanical properties of osteoarthritic joints and the biological behavior of chondrocytes. The results showed that PES with an intensity of 10 mA and a frequency of 4 Hz increased the cross-sectional area of muscle fibers, prevented muscle atrophy and loss of function, and restored the mechanical properties of muscle tissue. PES also effectively increases the resistivity of knee osteoarthritis cartilage tissue, as well as the elastic modulus of cartilage, which can enhance the biomechanical characteristics of cartilage tissue. PES also promoted the metabolic activity of chondrocytes and increased cartilage matrix synthesis, thereby improving the overall structure and mechanical properties of cartilage tissue. Additionally, cellular experiments showed that 5 consecutive days of 800 mV PES significantly increased the expression level of Piezo1 gene in chondrocytes. At the same time, the expression of type II collagen and transforming growth factor beta increased, while the expression of matrix metallopeptidase 13 decreased. These changes favored the promotion of cartilage matrix synthesis. This has a positive effect on protecting and improving joint health and reducing the impact of osteoarthritis, and is important for understanding the mechanism of action of PES on chondrocytes and the development of related therapeutic strategies.