The aim of the present study was to evaluate the influence of several experimental pretreatment crosslinker solutions on the resin polymer-dentine interface created using a representative universal adhesive system, by means of microtensile bond strength testing (µTBS), nanomechanical properties and ultramorphology confocal laser scanning microscopy (CLSM). Five experimental solutions containing different flavonoids were applied as dentine pretreatment after acid etching. A control pretreatment group containing no flavonoid was also employed. A representative modern universal adhesive was then applied, followed by a 3 mm thick composite built up. Specimens were sectioned into sticks and submitted to a µTBS test or nanoindentation analysis along the interface (24 h or 25,000 thermocycles). The ultramorphology of the polymer-resin interface was also evaluated using CLSM. The results were analyzed using two-way ANOVA and Bonferroni’s post hoc test (α = 0.05). All flavonoids improved short- and long-term µTBS values (p < 0.01), while only some specific such solutions improved the nanomechanical properties (p < 0.05) and preserved the structural morphology of the interface after aging. Pretreatment of acid-etched dentine using specific flavonoid-containing solutions may be a promising approach to improve both the nanomechanical properties and the durability of modern universal adhesive systems.