We aimed to determine the effect of vibration frequency and direction on upper-limb muscle activation using a handheld vibrator. We recruited 19 healthy participants who were instructed to hold a handheld vibrator in their dominant hand and maintain the elbow at 90° flexion, while vertical and horizontal vibrations were applied with frequencies of 15, 30, 45, and 60 Hz for 60 s each. Surface electromyography (EMG) measured the activities of the flexor digitorum superficialis (FDS), flexor carpi radialis (FCR), extensor carpi ulnaris (ECU), extensor carpi radialis (ECR), biceps, triceps, and deltoid anterior muscles. EMG changes were evaluated as the difference in muscle activity between vibration and no-vibration (0 Hz) conditions. Muscle activity was induced under vibration conditions in both vertical and horizontal (p < 0.05) directions. At 45 Hz, FDS and FCR activities increased during horizontal vibrations, compared with those during vertical vibrations. ECU activity significantly increased under 15-Hz vertical vibrations compared with that during horizontal vibrations. Vibrations from the handheld vibrator significantly induced upper-limb muscle activity. The maximum muscle activations for FDS, ECR, ECU, biceps, and triceps were induced by 45-Hz horizontal vibration. The 60-Hz vertical and 30-Hz horizontal vibrations facilitated maximum muscle activations for the FCR and deltoid anterior, respectively.