Objective This paper aimed to study the effect of ankle joint muscles strength loss on injured and healthy side knee joint muscles in a gait cycle in patients with chronic ankle instability (CAI). Methods The study established the inverse dynamic models of CAI patients and healthy people. Different degrees of ankle muscles strength loss were simulated by changing the muscles’ maximum isometric contraction force, and the study analyzed the changes of peak muscle strength and cumulative muscle strength of knee joint during a gait cycle . Results The loss of plantar flexor muscle strength in CAI patients also affects the quadriceps and hamstring muscles of the injured side and the healthy side. The loss of dorsal flexor muscle strength mainly affects the hamstring muscles of the injured side and the healthy side. In CAI patients, the muscle cumulative load of knee joint muscle on the affected side and the healthy side increased, and four different models of loss of muscle strength of the ankle joint showed that the cumulative load of quadriceps femoris on the affected side was greater than that on the healthy side (for example, 50% of muscle strength, at least more than 35.41 N·s). The cumulative load of hamstring muscle of the healthy side was greater than that of the affected side (50% of muscle strength as an example, at least more than 34.00 N·s). Conclusions CAI will not only affect the patients’ injured side of the knee muscle strength, but also affect the patients' healthy side’s, and different ankle muscle strength loss affects the knee muscle strength with different degrees in different phases. Strengthening the muscle strength of the ankle joint and protecting two sides knee joints muscles may have a positive effect on the rehabilitation of CAI.