Background: Non-invasive restoration of tooth enamel is a topic of high relevance in dental material sci- ence. Multiple approaches have been proposed to reach optimum reconstruction results. The current study was performed to evaluate the cross-sectional microhardness besides mineral quality and content in ar- tificially induced carious enamel after treatment with hydroxyapatite-chitosan (HAp-CS) nanocomposite gel. Methods: Artificially carious lesions were induced by immersion of teeth in acidic carboxymethyl cellulose gel (pH 4.95–5) for 24- and 72-hours periods. Two different compositions of HAp-CS nanocomposite hy- drogel were prepared with two different ratios 50/50 (%) and 70/30 (%), respectively. Additionally, sodium fluoride gel (10 0 0 ppm concentration) was prepared and used as reference. Gels were applied to cari- ous lesions twice/day for 3 min/each. After 45 days of application, surface morphology, energy dispersive x-ray spectroscopy, micro-Raman analysis in addition to cross-sectional microhardness were evaluated. Statistical analysis was performed using two-way ANOVA and Tukey’s post hoc statistical tests. Results: Surface morphological evaluation of treated surfaces showed obliteration of surface irregularities. Groups demineralized for 24 hours and treated with 70/30 (HAp-CS) showed highest significant cross- sectional-microhardness ( P ≤0.05). Evaluated subsurface cross-sectional microhardness showed better mineral quality for groups demineralized for 24 hours and treated with HAp-CS nanocomposite gels. Conclusions: Nanocomposite gel with 70/30 (HAp-CS) could efficiently improve cross-sectional microhard- ness and both minerals composition and quality for lesions demineralized for 24 hours. More severely induced lesions, as demineralized for 72 hours, need more powerful agent compositions and/or prolonged application protocols for improvement.