The study was conducted to investigating the effect of α-tocopherol acetate on heat shock protein 70 (Hsp70), oxidative stress, and antioxidant status during periparturient period in medium body condition score crossbred cows. Twenty crossbred Karan Fries cows with confirmed pregnancy were selected 2 months before expected date of calving. The cows were randomly distributed in to two groups: 10 cows were kept as control and 10 were supplemented with α-tocopherol acetate during dry period for 2 months. Blood samples were collected at -20, -10, -5, 0, 5, 10, and 20 days in relation to the expected date of calving. Superoxide dismutase, catalase, and total immunoglobulin were significantly higher (P < 0.01) in treatment as compared to control cows. Heat shock protein 70 and thiobarbituric acid reactive substance levels were significantly lower (P < 0.01) in the treatment cows than their counterpart. Treatment with α-tocopherol acetate during dry period resulted in reduced oxidative stress, heat shock protein Hsp70 levels, improved antioxidant, and improved immunity status indicating beneficial effect of α-tocopherol acetate treatment.