This study compared the effect of novel nano-based irrigants, Nano-Magnesium Oxide (Nano-MgO) and Nano-Silver Fluoride (Nano-AgF), to the gold standard 2.6% sodium hypochlorite (NaOCl) on canal cleanliness and smear layer removal. Thirty-six freshly extracted, single-rooted human mandibular premolars were selected, divided into three groups (n=12) and received either Nano-MgO (Group 1), Nano-AgF (Group 2), or NaOCl (Group 3) irrigating solutions. After root canal instrumentation and irrigation, each sample was longitudinally sectioned into two halves. One half underwent scanning electron microscope (SEM) analysis to assess smear layer removal effectiveness across coronal, middle, and apical sections of the canal. The other half was examined under a stereomicroscope equipped with a high-resolution camera to quantify the percentage of remaining debris in each section. Stereomicroscopic imaging of canal cleanliness revealed no significant difference between irrigating solutions in the coronal section. In the middle and apical sections, Nano-MgO irrigation resulted in a significantly higher percentage of remaining debris compared to both Nano-AgF and NaOCl. scanning electron photomicrograph showed significantly greater open dentinal tubule percentages, indicating better smear layer removal, in both coronal and middle sections for both Nano-MgO and Nano-AgF compared to NaOCl. In the apical section, both novel irrigating solutions (Nano-MgO and Nano-AgF) demonstrated a slight improvement over NaOCl, but the difference was statistically significant.