In view of the need for aesthetics, restorations of teeth will typically be completed using tooth colored restorative materials. With the advent of biomimetic restorative materials, such as glass ionomer cements (GIC), much greater emphasis is now being placed on how well such materials can resist the challenge of acids that are present in foods and drinks, or gastric contents that are regurgitated. This laboratory study compared the dissolution and behavior of five GIC materials (GC Fuji® VII, GC Fuji® Bulk, GC Fuji® IX Fast, Fuji® IX Extra and GC Equia® Forte Fil) when exposed to three acids (citric acid, phosphoric acid and lactic acid), versus ultrapure deionized water, which was used as a control. Discs of each material GIC were submerged in solutions and percentage weight changes over time determined. Subsequently, the GIC materials were also placed as a part of standardized Class II sandwich restorations in bovine teeth (n = 20), and submerged in the solutions, and the extent of GIC dissolution and protection of the adjacent tooth was scored. Weight loss increased with time and with acid concentration. Overall, the most soluble material was GC Fuji® IX Extra, while GC Fuji® IX Fast and GC Fuji® Bulk were less soluble, and the least soluble material was GC Equia® Forte Fil. The most destructive solution for both the discs and for GIC restorations in teeth was 10% citric acid, while the least destructive acid was 0.1% lactic acid. The more recent GIC materials GC Fuji® Bulk and GC Equia® Forte Fil showed increased acid resistance over the older GIC materials, and this further justifies their use in open sandwich Class II restorations in more hostile environments.