BACKGROUND Miswak is a form of chewing stick used to clean teeth in different parts of the world, including Saudi Arabia. We present a description of the effects of miswak derivatives, namely toothpaste, mouthwash, and brushing sticks, on the mean color changes (DE00), compressive fracture resistance values, and fracture modes of polymer-based computer-aided design (CAD) and computer-aided manufactured (CAM) prosthetic materials. MATERIAL AND METHODS Eighty-one rectangular-shaped samples were prepared from lithium disilicate glass-ceramic (IPS e.max CAD), zirconia-reinforced lithium silicate (Vita Suprinity), and monochromatic tooth-colored feldspar (Vitablocs Mark II) CAD/CAM ceramics. The color parameters were recorded using spectrophotometer before and after exposing the specimens to the different miswak oral hygiene derivatives for 15 days. Compressive fracture resistance values and fracture types were also assessed, and statistical analysis was performed. RESULTS Vita Suprinity and Vitablocs Mark II miswak sticks had the highest ΔE₀₀ values. Moreover, miswak mouthwash had the lowest ΔE₀₀ values, with significant differences among groups. IPS e.max CAD miswak sticks had the highest mean values of compressive fracture. Vitablocs Mark II had the lowest values for mouthwash and toothpaste. Significant differences were found within the IPS e.max CAD group. Reparable fractures were found in IPS e.max CAD, while semi-reparable fractures were seen in other groups. CONCLUSIONS Most ΔE₀₀ values were within the acceptable clinical range, with IPS e.max CAD showing superior color stability. The mouthwash group showed minimal ΔE₀₀. IPS e.max CAD had the highest mean compressive fracture resistance values with reparable fracture types.