Palmar hyperhidrosis represents a condition with a significant cosmetic and psychological burden. Various treatment modalities are available; however, searching for newer options to meet patients' needs and expectations is encouraged. The study aimed to evaluate the efficacy of photodynamic therapy (PDT) for treatment of primary palmar hyperhidrosis. Two different photosensitizers for PDT were evaluated: eosin Y, and methylene blue. The study focused on the clinical efficacy, patient's satisfaction, and the time and number of sessions needed to achieve a satisfactory response. Twenty patients with primary palmar hyperhidrosis were enrolled in a single-center clinical study. Patients were treated with PDT for a maximum of eight sessions. Two photosensitizers were tested: eosin Y, and methylene blue for the right and left hand, respectively. The Hyperhidrosis disease severity scale (HDSS), and Sweating Intensity Visual Scale of Minor's test were used for assessment. Photodynamic therapy effectively reduced the severity scores of hyperhidrosis with comparable results between the two photosensitizers. The treatment effect was maintained up to 3 months after the last procedure. Photodynamic therapy is a good treatment option for primary palmar hyperhidrosis with results maintainable for 3 months after the treatment end.