Leaf spot is one of the most important cassava diseases. Nanotechnology can be applied to control diseases and improve plant growth. This study was performed to prepare chitosan (CS) nanoparticle (NP)-loaded salicylic acid (SA) or silver (Ag) by the ionic gelation method, and to evaluate their effectiveness on reducing leaf spot disease and enhancing the growth of cassava plants. The CS (0.4 or 0.5%) and Pentasodium triphosphate (0.2 or 0.5%) were mixed with SA varying at 0.05, 0.1, or 0.2% or silver nitrate varying at 1, 2, or 3 mM to prepare three formulations of CS-NP-loaded SA named N1, N2, and N3 or CS-NP-loaded Ag named N4, N5, and N6. The results showed that the six formulations were not toxic to cassava leaves up to 800 ppm. The CS-NP-loaded SA (N3) and CS-NP-loaded Ag (N6) were more effective than the remaining formulations in reducing the disease severity and the disease index of leaf spot. Furthermore, N3 at 400 ppm and N6 at 200, 400, and 800 ppm could reduce disease severity (68.9–73.6% or 37.0–37.7%, depending on the time of treatment and the pathogen density) and enhance plant growth more than or equal to commercial fungicide or nano-fungicide products under net-house conditions. The study indicates the potential to use CS-NP-loaded SA or Ag as elicitors to manage cassava leaf spot disease.