This study investigated the effect of three remineralizing agents on improving white spot lesions (WSLs). This clinical trial included children who had at least one WSL on anterior teeth of upper or lower jaws. The participants were randomly assigned to 4 groups by treatment: 1) a cream containing casein phosphopeptide-amorphous calcium phosphate and fluoride (MI Paste Plus); 2) a cream containing hydroxyapatite and fluoride (Remin Pro); 3) a 2% sodium fluoride gel; and 4) usual home care (control). The treatment was performed for 3 times over 10 days using special trays for retaining remineralizing agents. The area and mineral content of WSLs were measured at baseline (T1) and 1 day after finishing treatment (T2). Blinding was applied for outcome assessment. Eighty patients were assigned to MI Paste Plus, Remin Pro, NaF or control groups. The application of all remineralizing agents caused a significant decrease in area and a significant increase in mineral content of WSLs (p<0.05), whereas the control patients did not experience any significant alteration (p>0.05). At T2, the area of WSLs was significantly lower in three experimental groups compared to the control group (p=0.023), but between-group difference in mineral content of WSLs failed to achieve statistical significance (p=0.08). The in-office application of either MI Paste Plus or Remin Pro was as effective as 2% NaF for reducing area and increasing mineral content of WSLs. MI Paste Plus and Remin Pro could be recommended as suitable alternatives to NaF for managing WSLs.