Aims and background: The efficacy of self-assembling peptide P11-4 in combination with calcium-phosphate-based remineralization agents in remineralizing caries-like lesions in primary enamel was evaluated using a 21-day pH cycling experiment by Vickers microhardness [Vickers hardness number (VHN)] and scanning electron microscopy (SEM). Materials and methods: A total of 120 primary enamel samples were made to undergo a demineralization cycle to produce caries-like lesions. They were divided into six groups, namely negative control (NC), positive control (P11-4), and four interventional groups in which each of the following calcium-phosphate-based agents were used in combination with P11-4—calcium sucrose phosphate (CSP), bioactive glass (BG), casein phosphopeptides, and casein phosphopeptides with fluoride. A 21-day pH cycling experiment was carried out with alternating demineralization and remineralization phases. The enamel samples were analyzed at baseline, post production of caries-like lesions, and post 21-day pH cycling using Vickers microhardness and SEM. Results were statistically analyzed using repeated measures of analysis of variance (ANOVA), keeping the level of significance at 0.05. Results: Supplementing P11-4 with calcium-phosphate-based agents improved the surface hardness of the demineralized primary enamel samples, among which the fluoridated milk protein-based remineralization agent yielded a statistically significant improvement. Conclusion: P11-4 promoted the regeneration of incipient caries-like lesions. However, there is added benefit when this peptide is used in combination with a fluoridated calcium-phosphate-based agent. Clinical significance: This study would help the clinician compose an effective regimen for the patient to follow at home posttreatment with P11-4, in-office treatment.