Introduction: Chronic ankle instability (CAI) is described as the patient’s sense of an abnormal ankle, which is characterized by a combination of symptoms such as recurrent sprains, discomfort, edema, or activity avoidance. Talocrural thrust manipulation (TCTM) is a manual treatment technique that includes applying a manual push to a specific motion segment, often in the form of a joint glide. The study aimed to find out the dosimetry and effect of TCTM on the range of motion (ROM) and quality of life (QoL) in subjects with CAI. Materials and Methods: Forty subjects fulfilling the selection criteria were included in the study, with single group repeated measures design. A talocrural thrust is given to the ankle and outcomes were assessed during 1st week, 2nd week, and 3rd week after the intervention, and the scores were recorded. Results: The group was ranging from 13 to 22, with a mean and standard deviation (SD) of 16.15 ± 2.28. After 1 week, showed an increase in the range of 17–29, with a mean and SD of 22.40 ± 2.75. Similarly, for 2 weeks, the range increased to 24–32 with a mean and SD of 29.53 ± 1.71 after 2 weeks. However, the range was found to have increased to 31–34, with a mean and SD of 32.35 ± 0.70, and found to be statistically significant (P < 0.001). Conclusion: TCTM is effective in improving ROM and QoL in people who have persistent ankle instability. Talocrural thrust manipulation technique stimulates the proprioceptive awareness which is often impaired in chronic instability subjects targeting the joints with specific thrust to treat pain and dysfunction and the consistency of the movement underlying the tissues which is more crucial in identifying the restrictions of the joint. The following core competencies are addressed in this article: Medical knowledge, Patient care, Systems-based practice