Silica is widely used in the oral care formulations to act as an abrasive and to give the products its distinct physical properties. In this study, silica particles were synthesized using a co-condensation of tetraethyl orthosilicate with a series of functional silane compounds [(3-mercaptopropyl)trimethoxysilane, (3-glycidyloxypropyl)trimethoxysilane, and (3-acryloxypropyl)trimethoxysilane)]. The surface of the particles based on tetraethyl orthosilicate and (3-glycidyloxypropyl)trimethoxysilane was then further modified with 3-aminophenylboronic acid. Commercial Aerosil R972 Pharma silica particles were also coated with chitosan. Additionally, commercially available (3-maleimido)propyl-functionalized silica particles were used in this study. All these functionalized silica particles were incorporated into toothpaste formulations, and their retentive properties were tested on ex vivo sheep tongue mucosa models using fluorescent microscopy-based flow-through techniques. Those surfaces with chitosan, phenylboronic acid, and acryloyl groups were shown to provide a significant improvement in the retention of the oral care formulations during the retention testing. The retention of toothpastes containing silica functionalized with maleimide and thiol groups was also superior compared to that of unmodified silica particles. This study synthesized and tested a range of silica particles and demonstrated that the functionalized silica incorporated into toothpastes can significantly improve the retention of these formulations on oral mucosal surfaces.