Objective To study the effect of strength loss in ankle muscles on injured and healthy side of knee joint muscles in patients with chronic ankle instability (CAI). Methods The inverse dynamic models of CAI patients and healthy subjects were established. The strength loss of ankle muscles at different degrees was simulated by changing the maximum isometric contraction force of muscles, and the change patterns for peak muscle strength and cumulative muscle strength of knee joints during a gait cycle were analyzed. Results The strength loss of plantar flexor muscle in CAI patients would affect both the quadriceps and hamstring muscles of the injured side and the healthy side. The strength loss of dorsal flexor muscle mainly affected the hamstring muscles of the injured side and the healthy side in CAI patients. The cumulative load on the affected side and the healthy side of knee joint muscles increased, and models with different strength loss of ankle muscles showed that the cumulative load of quadriceps femoris on the affected side was greater than that on the healthy side. The cumulative load on hamstring muscle of the healthy side was greater than that of the affected side. Conclusions CAI will not only affect the patients’ injured side of knee joint muscle strength, but also affect their healthy side. Strengthening the ankle muscles and protecting the bilateral knee muscles may have a positive effect on the rehabilitation of CAI.