<p>This investigation sought to evaluate the comparative influence of different irrigation activation protocols—ultrasonic, sonic, XP-Endo Finisher, and manual dynamic activation (MDA)—on the nanohardness, elastic modulus, flexural strength, and elemental composition of root dentin. Fifty intact single-rooted human mandibular premolars were decoronated 15&#xa0;mm from the apex and instrumented using the ProTaper Next rotary file system (Dentsply Sirona, USA) under standardized irrigation protocols. Specimens were randomized into five groups (<i>n</i> = 10/group): ultrasonic activation, sonic activation, MDA, XP-Endo Finisher, and a non-activated control. Nanohardness and elastic modulus were measured, while flexural strength was evaluated using a three-point bending test. Elemental composition analysis was conducted with energy-dispersive X-ray spectroscop. Statistical comparisons were performed using one-way ANOVA followed by Tukey’s HSD post hoc tests in SPSS v26 (IBM, USA), with significance set at <i>p</i> &lt; 0.05. Statistical comparisons revealed statistically insignificant differences in nanohardness / GPa (F = 1.207, <i>p</i> = 0.321) and flexural strength / GPa (F = 0.808, <i>p</i> = 0.527) across groups. However, elastic modulus / MPa exhibited intergroup variation (<i>p</i> &lt; 0.05), with post hoc Tukey’s tests indicating higher values in the sonic activation group compared to ultrasonic activation and XP-Endo Finisher groups. EDS analysis showed no significant differences in oxygen, calcium, or phosphorus content (<i>p</i> &gt; 0.05). Irrigation activation protocols had no significant effect on root dentin nanohardness, flexural strength, or elemental composition; however, sonic activation demonstrated a significantly higher elastic modulus. These findings highlight the mechanical stability of dentin across various activation methods.</p>