This study aimed to compare the effect of simulated brushing on one Nano resin-coated glass ionomer (GI) (EF; Equia forte fil/Equia forte coat, GC Corp., Tokyo, Japan) and one Nano zirconia-reinforced GI (ZI; Zirconomer Improve, Shofu, Inc., Kyoto, Japan). One hundred and forty specimens were prepared and divided into two groups: EF and ZI. The Vickers Hardness Number (VHN) and surface roughness (Ra) were measured before and after simulated brushing of the specimens with water or with water and Colgate Total 12 (CT12) for 5,000, 10,000, and 20,000 cycles. Regardless of condition, EF and ZI showed statistically significant differences of mean VHN: 146.90 ± 36.66; 110.30 ± 13.73, (p-value < 0.001), and mean Ra: 0.290 ± 0.089μm; 0.247 ± 0.085μm (p-value ≤ 0.05), respectively. For both EF and ZI, repeated measures analysis of variance (ANOVA) revealed a statistically significant difference of mean VHN (p-value ≤ 0.05) in all cycles’ intervals with CT12, but only at 20,000 cycles with water and in Ra (p-value ≤ 0.05) in all conditions compared to the control group. A post-hoc Tukey’s test revealed a statistically significant difference of mean VHN in water vs. CT12 (p-value ≤ 0.001) for both EF and ZI in all conditions. The EF showed higher mean surface hardness and higher mean surface roughness as compared to the ZI. Both the EF and ZI specimens demonstrated resistance to the softening when being subjected to the simulated tooth brushing procedure equivalent to about 1 year of clinical use.