Apart from producing high bond strength to tooth enamel and dentin, a dental adhesive with biotherapeutic potential is clinically desirable, aiming to further improve tooth restoration longevity. In this laboratory study, an experimental two-step universal adhesive, referred to as Exp_2UA, applicable in both the etch-and-rinse (E&R) and self-etch (SE) modes and combining a primer, containing 10-methacryloyloxydecyldihydrogen phosphate as a functional monomer with chemical binding potential to hydroxyapatite, with a bioglass-containing hydrophobic adhesive resin, was multifactorially investigated. In addition to primary property assessment, including measurement of bond strength, water sorption, solubility, and polymerization efficiency, the resultant adhesive-dentin interface was characterized by transmission electron microscopy (TEM), the filler composition was analyzed by energy-dispersive X-ray spectroscopy, and the bioactive potential of the adhesive was estimated by measuring the long-term ion release and assessing its antienzymatic and antibacterial potential. Four representative commercial adhesives were used as reference/controls. Application in both the E&R and SE modes resulted in a durable bonding performance to dentin, as evidenced by favorable 1 year aged bond strength data and a tight interfacial ultrastructure that, as examined by TEM, remained ultramorphologically unaltered upon 1 year of water storage aging. TEM revealed a 20 μm thick hydrophobic adhesive layer with a homogeneous bioglass filler distribution. Adequate polymerization conversion resulted in extremely low water sorption and solubility. In situ zymography revealed reduced endogenous proteolytic activity, while Streptococcus mutans biofilm formation was inhibited. In conclusion, the three-/two-step E&R/SE Exp2UA combines the high bonding potential and bond degradation resistance with long-term ion release, rendering the adhesive antienzymatic and antibacterial potential.