Background: To evaluate the impact of incorporating chitosan/hydroxyapatite composite nanoparticles (CT/HAP NPs) into a universal adhesive on its bonding effectiveness to caries-affected dentin (CAD) and its in vitro bioactivity. Methods: CT/HAP NPs (50:50 by weight) were synthesized via a one-step co-precipitation method. All-Bond universal adhesive was modified with either 0.5 wt% or 1 wt% CT/HAP NPs, yielding three groups: unmodified control, 0.5 wt%, and 1 wt% CT/HAP. Forty-eight molar teeth (4 teeth per group) were used to prepare 240 bonded beams using either etch-and-rinse (ER) or selective-etch (SE) mode ( n = 20 bonded beams per group). Micro-tensile bond strength (µTBS) test was conducted using a universal testing machine after 24 h and 6 months of storage in simulated body fluid (SBF). Fifteen adhesive discs (5 mm x 1 mm) ( n = 5) were examined using an environmental scanning electron microscope combined with an energy-dispersive X-ray spectroscopy ( ESEM/EDX ) following storage in SBF for 1 day and 28 days to assess bioactivity and Ca/P ratio. Wettability, pH, and degree of conversion (DC) were assessed using a digital light microscope, a pH meter, and Fourier transform infrared (FTIR) spectroscopy, respectively. µTBS and wettability data were investigated utilizing multilevel ANOVA, while pH and DC were evaluated utilizing one-way ANOVA; Tukey’s post hoc test was applied for pairwise multiple comparisons. The significance level was set at ( p < 0.05). Results: The 1 wt% CT/HAP group exhibited significantly higher µTBS at 24 h (ER: 37.50 ± 6.90 MPa; SE: 32.52 ± 6.61 MPa) and at 6 months (ER: 41.81 ± 7.64 MPa; SE: 42.10 ± 7.23 MPa) than the 0.5 wt% CT/HAP and control groups. Adhesives containing CT/HAP NPs showed improved surface mineral deposition and higher Ca/P ratios compared to control. Wettability, pH, and degree of conversion revealed no significant changes. Conclusions: Incorporating chitosan/hydroxyapatite composite nanoparticles into an ultra-mild universal adhesive enhanced its bonding efficacy to caries-affected dentin as well as its bioactive potential, without jeopardizing the physical and chemical properties of the adhesive.