Introduction Although seborrheic dermatitis (SD) is not lethal, it has a significant impact on the quality of life. Many cases of SD are managed with ketoconazole, but luliconazole has shown an equivalent or lower minimum inhibitory concentration (MIC), but not many studies have been done for its efficacy and safety in SD. With this in mind, we set out to conduct a study comparing the effectiveness, safety, and tolerability of Lulican™ (luliconazole 1% + salicylic acid 3% + ZPTO 1%) shampoo and Ketoconazole (Ketoconazole 2% + ZPTO 1%) shampoo in the treatment of SD. Materials and methods In this prospective, randomized, multi-center study, mild to moderate scalp SD patients were prescribed Lulican™ or Ketoconazole shampoo three times a week for a duration of four weeks. Effectiveness assessment was done with the Seborrheic-Dermatitis-Severity-Score (SDSS) and Physician-GlobalAssessment (PGA), and quality of life was assessed with the help of the Scalpdex-23 questionnaire. Results At four weeks, 68% and 57.9% reduction was seen in SDSS in Lulican™ and Ketoconazole shampoo, respectively. Moreover, 58% and 44% of patients achieved excellent to moderate responses as per PGA with Lulican™ and ketoconazole shampoo, respectively. For safety, no statistical difference was reported, but product tolerability and subjective cosmetic acceptability were significantly better in the Lulican™ group as compared to the Ketoconazole group at the end of four weeks. The mean Scalpdex-23 score at week four was reduced by 35.7% and 21.1% in Lulican™ and ketoconazole groups, respectively (p<0.05). Conclusion While both treatments were successful in alleviating SD symptoms and were well tolerated, Lulican™ stood out as a preferred treatment option due to better quality of life (QoL) improvement in SD.