The aim of this work was to reduce microleakage in giomer restorations by using innovative materials in both adhesive systems and light-cured dental giomer. Two adhesive systems with different primers were investigated. The innovative compounds in the primers were acrylic acid (AA)/itaconic acid (IA) copolymer modified with methacrylic groups and AA/IA/N-acryloyl-L-leucine copolymer grafted with methacrylic groups. In addition, the investigated new giomer G contains a pre-reacted glass based on the latter copolymer. The commercial Beautifil II giomer and the FL-Bond II adhesive system were used for comparison. Microleakage was evaluated by determining the scores and percentages of dye penetration lengths after thermocycling of a series of light-cured dental giomer restorations performed on 42 premolars extracted for orthodontic reasons. A lower microleakage value was recorded for the adhesive system containing the AA/IA/N-acryloyl-L-leucine copolymer grafted with methacrylic groups than for the commercial adhesive, which was in substantial agreement with SEM and AFM investigations. In this case, remarkable dentin sealing and a strong adhesion at the giomer restoration�tooth interface was observed, and the innovative adhesive was proven to be promising for dental applications.