(1) Background: Silicon (Si) and nitric oxide (NO) have been proven to protect against cellular injury caused by stress conditions, mostly by salinity and water stress in agriculture. (2) Methods: The goal was to study the effect of soil applications of NO, Si, and their combination (Si+NO) on the response of Myrobalan 29C rootstocks (Prunus cerasifera Ehrh.) subjected to water stress and well-watered conditions. (3) Results: The results showed that water stress decreased growth parameters (i.e., leaf area, shoot dry weight, root fresh weight, shoot fresh weight, root dry weight, and relative shoot diameter), physio-biochemical parameters (i.e., chlorophyll and relative water content in leaves), and leaf and root minerals (i.e., P, Ca, Fe, and Zn in leaves and N, K, Ca, and Zn in roots), compared to well-watered plants. Under these conditions, all treatments mitigated the detrimental effects of water stress on Myrobalan 29C rootstocks, being the most effective the Si+NO treatment. (4) Conclusions: These findings briefly highlight that the combination of silicon and nitric oxide may provide greater tolerance to water stress in Myrobalan 29C rootstocks.