Solving the fungicide resistance of the rice blast fungus Pyricularia oryzae (P. oryzae) is essential for rice production in the Mekong Delta region of Vietnam. Thus, this study aimed to investigate fungicide resistance and evaluate Ag/SiO2 nanocomposites for controlling the chemical resistance of P. oryzae. Here, a total of 30 P. oryzae isolates was collected, and most of the isolates exhibited conidia with pyriform and short pyriform. The sensitivity in vitro of all isolates was measured against those three chemicals via the poisoning method. Furthermore, the EC50 and the resistance factor (RF) were evaluated for 12 days after inoculation. The obtained results revealed that all of the P. oryzae isolates were sensitive to tricyclazole; to chlorothalonil, 67% of them were sensitive, while the rest 33% were medium-sensitive. To azoxystrobin, 17% of them were sensitive, 57% were medium-sensitive, 23% were resistant, and the rest, 3%, were highly resistant. Subsequently, the antifungal activity of the Ag/SiO2 nanocomposites against two P. oryzae resistance isolates (labeled TM4 and TAT2) was determined. Interestingly, Ag/SiO2 nanocomposites exhibited a 100% inhibition effect for mycelial growth of TM4 and TAT2 isolates at a concentration of 60 µg/mL because Ag/SiO2 nanocomposites can activate the hyphae of P. oryzae to lose their typical structure (breaking filaments and damaging cell wall integrity). Overall, this study confirms the resistance of P. oryzae isolates to azoxystrobin and chlorothalonil and also highlights the potential of Ag/SiO2 as an alternative solution to control blast rice disease.