Objectives This study evaluated and compared the effect of silver diamine fluoride (SDF) and silver-modified atraumatic restorative treatment (SMART) sealants for the treatment of initial carious lesions of permanent molars affected by molar incisor hypomineralization (MIH). Methods One hundred and twelve hypomineralized permanent molars with ICDAS 1 or 2 lesions were selected in 48 children. The teeth were randomized into SDF and SMART sealant groups (n = 56 teeth/group) in a split-mouth fashion. Hypersensitivity, formation of caries, and enamel breakdown were evaluated in both groups. Hypersensitivity was assessed by Schiff Cold Air Sensitivity Scale (SCASS), and clinical assessments of SMART sealants were performed according to modified USPHS criteria at 1, 6, and 12 months. The data were analyzed statistically using Fisher's exact test, Kaplan-Meier analysis, Mann-Whitney U test, and Friedman test. Results Twenty-six hypomineralized molars with marked baseline hypersensitivity showed significantly lower SCASS scores at all evaluation periods (p < 0.001). There was no significant difference in hypersensitivity scores between the groups at the repeated applications of SDF at 1, 6, and 12 months. The cumulative survival rates of SMART sealants on occlusal and palatal surfaces were 88.7% and 58.8%, respectively. Conclusions In hypomineralized molars, both SDF and SMART sealants showed favorable short-term prevention against dental caries while providing effective desensitization. Marginal discoloration was the most common side effect of the SMART sealants as a result of SDF application. Clinical Significance Both SDF and SMART sealants showed similar short-term effectiveness as non-aerosol procedures in arresting enamel caries and reducing hypersensitivity in hypomineralized molars.