Treatment of the periorbital dark circles (PDCs) is a current challenge, with most treatment methods failing to yield promising results. The effectiveness of two common methods for periorbital dark circle treatment was compared in 28 patients with PDC. The patients were randomly divided into two groups of equal numbers: the first group received carboxy therapy, and the second group fractional 10,64 nm Q-switched Nd:YAG laser. In the carboxy therapy group, the treatment was performed six times, with 1-week intervals between sessions. In the group treated by Nd:YAG laser, the treatment was conducted in four sessions, with 1-month intervals between sessions. The results were evaluated through biometric evaluation, scoring on the visual analog scale (VAS) by both physicians and patients, and patients' satisfaction. Side effects of the treatments were also evaluated. The results showed that both carboxy therapy and Nd:YAG laser are effective in the treatment of periorbital dark circles, but carboxy therapy is significantly more effective. An increase in the skin lightness and a decrease in the melanin content of the periorbital skin was observed in the group receiving carboxy therapy, and these changes were more pronounced in this group compared to the group of Nd:YAG laser. In addition, side effects, such as erythema and post-inflammatory hyperpigmentation, were less in carboxy therapy than in Nd:YAG laser. Furthermore, the procedure was less expensive and easier to perform compared to Nd:YAG laser. Carboxy therapy is significantly more effective than Nd:YAG laser in PDC treatment.Trial registration: IRCT20080901001159N24.