Striae distensae are atrophic scars that are often cosmetically distressing. The efficacy of fractional carbon dioxide (CO2) laser and platelet-rich plasma (PRP) in treating striae individually has been evaluated previously. However, not many studies described the combined efficacy of both. The aim of this study was to compare the efficacy and safety of fractional CO2 laser alone and in combination with PRP. Twenty-four patients with striae presenting bilaterally in the abdomen, upper limbs, and lower limbs were included. PRP was prepared by double-spin method and cell count was done to ensure at least fourfold concentration of platelets. The patients were treated CO2 laser on both sides and PRP on the left side along with laser, every month for three sessions. Digital photography and dermoscopy were done at baseline, every treatment session, and 6 months after treatment. Clinical improvement was assessed by comparing photographs and patient satisfaction before and after treatment. All patients showed improvement on both sides. In CO2-laser-treated patients, responses in 6 patients (25%) were moderate, 14 (56%) were good, and 4 (16.6%) were excellent. In CO2-laser and PRP-treated patients, responses in 5 patients (20.8%) were moderate, 11 (45.8%) were good, and 8 (33.3%) were excellent. Hyperpigmentation was the most common side-effect seen (19 patients) on both sides, which resolved spontaneously by 6 months. These results support the use of ablative CO2 fractional laser as effective and safe treatment modalities for striae. However, slightly better efficacy was noted with the addition of PRP.