This study aimed to evaluate chitosan (CS)-based formulations loaded with 5% sodium fluoride (NaF) and/or 10% nanohydroxyapatite (nHA) to remineralize the demineralized primary tooth enamel surface. Ninety enamel blocks were demineralized and were divided into six groups (n = 15): (1) CS-based hydrogel, (2) CS-based hydrogel loaded with NaF, (3) CS-based hydrogel loaded with nHA, (4) CS-based hydrogel loaded with NaF and nHA, (5) 5% NaF varnish, and (6) negative control with no intervention. After intervention, the specimens were pH cycled by 2 h immersion in demineralizing solution and 22 h immersion in remineralizing solution for 8 days. The remineralization effects were evaluated by Vickers microhardness measurements and field emission scanning electron microscopy coupled with energy-dispersive X-ray spectrometry (FESEM-EDS). The best mean ± SD percentage microhardness recovery in remineralized enamel (%REMH) was found in group 4 (56.90 ± 5.49). The %REMH of groups 2 (30.74 ± 3.51) and 5 (29.23 ± 5.65) were statistically the same (p = 0.943). FESEM images confirmed partial coverage of the porous demineralized enamel with a newly formed mineralized layer. Based on EDS findings, the Ca/P ratio values of the treated enamel surfaces with CS-based hydrogels ranged between 1.71 and 1.87, and the highest F content was noticed in group 2 (1.02 ± 0.03). Although, all tested CS-based hydrogels demonstrated the potential to repair demineralized enamel, nHA- and NaF-containing CS-based hydrogel showed the highest remineralization effect. We infer that this new hybrid hydrogel is a potentially useful dental material for tooth biomineralization.