AimTo assess and compare the antimicrobial efficacy of disinfectants on lithium disilicate ceramic (LDC) used in dental applications and shear bond strength (SBS) of LDC after using different conditioners hydrofluoric acid (HF), self-etching ceramic primers (SECP) and Neodymium-doped yttrium orthovanadate (Nd: YVO4). Materials and methodsOne hundred and twenty LDC discs were fabricated by auto-polymerizing acrylic resin using the lost wax technique. S. aureus, S. mutans, and C. albican were inoculated on thirty discs (n = 30 each). Each group was further divided into three subgroups based on different disinfecting agents used (n = 30) Group 1: Garlic extract, Group 2: Rose Bengal (RB) activated by PDT, and Group 3: Sodium hypochlorite (NaOCl). An assessment of the survival rate of microorganisms was performed. The remaining thirty samples were surface treated using three different LDC surface conditioners (n = 10) Group 1: HF + Silane (S), group 2: SECP, and Group 3: Nd: YVO4 laser+S. SBS and failure mode analysis were performed using a universal testing machine and stereomicroscope at 40x magnification, The statistical analysis was conducted using one-way ANOVA and Post Hoc Tukey test. ResultsGarlic extract, RB, and 2% NaOCl sample displayed comparable outcomes of antimicrobial potency against C. albicans, S aureus, and S. mutans (p > 0.05). Furthermore, SBS analysis showed HF+S, SECP, and Nd: YVO4+S exhibited comparable outcomes of bond strength (p > 0.05). ConclusionGarlic extract and Rose bengal activated by PDT can be contemplated as alternatives to the chemical agent NaOCl used for LDC disinfection. Similarly, SECP and Nd: YVO4 possess the potential to be used for the surface conditioning of LDC to improve the bond integrity with resin cement.