The objective of our study was to examine the effect of alpha-lipoic acid (ALA) on clinical and neurophysiologic outcomes after surgery for idiopathic carpal tunnel syndrome (CTS). We conducted a randomized, double-blind, placebo-controlled clinical trial in 20 adults diagnosed with idiopathic CTS after clinical and neurophysiologic assessment. Eligible participants took 600 mg ALA or placebo per day for 1 month before surgery, and for 2 months afterward. Further clinical and neurophysiologic assessments were undertaken immediately before surgical decompression, and at 12 weeks postoperatively with additional clinical assessments at the 4th and 8th week after surgery. Clinical outcome measures were taken by Boston Questionnaire score, the presence or absence of Tinel’s sign, and Phalen’s test findings. Median nerve conduction studies were also undertaken and interpreted according to Dumitru’s reference values. Nineteen patients completed the study; one member of the placebo group was lost during follow-up. There were significant improvements in clinical and neurophysiologic variables in the ALA treatment group, present even before surgery. Boston Questionnaire scores had improved significantly in both groups. In the ALA group, none of the participants had positive Phalen’s or Tinel’s signs at 12 weeks, and motor and sensory fiber latency and amplitude had significantly improved; in the placebo group, only the sensory distal latency had improved significantly. In conclusion, ALA administered 1 month before open decompression and for 2 months afterward improves the clinical and neurophysiologic outcomes after surgery.