We assessed the effectiveness of interferential current (IFC) and transcutaneous electrical nerve stimulation (TENS) therapies in the management of carpal tunnel syndrome (CTS) compared with splint therapy, a standard treatment modality for CTS. This was a prospective, single-blinded, single-center, randomized, three-group parallel intervention study of 3 weeks duration. Efficacy was examined in the third week after the end of treatments. Subjects were assigned randomly to one of three groups: group I patients received splint therapy, group II patients received TENS applied on the palmar surface of the hand and the carpal tunnel, and group III patients underwent IFC therapy applied on the palmar surface of the hand and the volar surface of the forearm. TENS and ICF treatments were applied five times weekly for a total of 15 sessions. Group 1 patients were stabilized with volar wrist splints for 3 weeks. The efficacy of the therapies was assessed before initiation of therapy and at 3 weeks after completion of therapy using a visual analog scale (VAS), a symptom severity scale, the functional capacity scale of the BCTQ, and measurement of median nerve motor distal latency (mMDL) and median sensory nerve conduction velocity (mSNCV). Groups were compared pairwise using the Mann-Whitney U test to identify the source of differences between groups. The Wilcoxon test was used to analyze changes in variables over time within a group. In the VAS, BCTQ, MDL, and mSNCV, no significant difference was observed between the groups (p > 0.05). In the VAS, BCTQ, and mSNCV, statistically significant improvements were detected in all groups (p < 0.05). There was no statistically significant difference between TENS and splint therapy with respect to improvement in clinical scores, whereas IFC therapy provided a significantly greater improvement in VAS, mMDL, and mSNCV values than splint therapy (VAS: 4.80 +/- A 1.18 and 6.37 +/- A 1.18; p = 0.001, mMDL: 3.89 +/- A 0.88 and 4.06 +/- A 0.61; p = 0.001, mSNCV: 41.80 +/- A 1.76 and 40.75 +/- A 1.48; p = 0.010). IFC therapy provided a significantly greater improvement in VAS, symptom severity, functional capacity, and mMDL and mSNCV values than TENS therapy (VAS: 4.80 +/- A 1.18 and 6.68 +/- A 1.42; p < 0.001, symptom severity: 2.70 +/- A 1.03 and 3.37 +/- A 1.21; p = 0.015, functional capacity: 1.90 +/- A 1.21 and 2.50 +/- A 0.78; p = 0.039, mMDL: 3.89 +/- A 0.88 and 4.06 +/- A 0.88; p = 0.003, and mSNCV: 41.80 +/- A 1.76 and 41.38 +/- A 1.78; p = 0.021). IFC may be considered a new and safe therapeutic option for the treatment of CTS.