The aim of the current study is to observe how different pediatric drugs and tooth brushing affect the color stability of different esthetic restorative materials. Three restorative materials (composite, compomer, and glass ionomer cement (GIC)) were each used to produce 72 specimens (10 mm × 2 mm). The specimens were divided into six groups and immersed in distilled water and five different pediatric drugs (amoxicillin, ibuprofen, ventolin, paracetamol, and multivitamins). Each group was divided into two subgroups (brushed and non-brushed). Over the course of two weeks, the specimens were agitated for one minute every eight hours. Color changes in all the specimens were evaluated using a spectrophotometer at 1 and 2 weeks. GIC showed a change in color that was significantly greater than that in all the other materials in each solution, except for those in amoxicillin. After a period of 1 to 2 weeks, the most noticeable change in color was detected in the amoxicillin composite and amoxicillin GIC unbrushed groups, and after 2 weeks, a significant difference was found in the ventolin GIC unbrushed group. The color stability of the restorative materials used in pediatric dentistry can be influenced by using popular liquid pediatric medications. GIC was the least color-stable material when subjected to liquid medications.