Background: PEEK is a polymer with lots of significant potentials making it an important candidate in dental applications, however strong durable bond of PEEK restorations with resin cement is still questionable. Aim: The aim of the present study is to evaluate the effect of different surface treatment protocols on the bond strength of PEEK surface with resin cement in comparison to Lithium Disilicate ceramic. Methodology: PEEK (P) and Lithium Disilicate discs (LD) were fabricated using CAD/CAM technique. A total of 40 samples were divided into four groups according to surface treatment protocol (n=10): Group (LD): hydrofluoric acid etching followed by silane application. Group (PP): 110 µm alumina particles sandblasting followed by Piranha solution acid etching. Group (PNsi): 110 µm alumina particles sandblasting followed by nano-silica coating and silane coupling agent respectively. Group (PN): 110 µm alumina particles sandblasting followed by nano-silica coating. All specimens underwent thermocycling. Micro-shear bond strength (μSBS) test was performed using a universal testing machine and the mode of failure was assessed using digital microscope. Surface roughness was assessed before and after surface treatment using optical profilometer. Results: statistically significant difference was found between the groups (P-value = 0.028, Effect size = 0.274). Pair-wise comparisons revealed that there was no statistically significant difference between (LD) and (PP); both showed the highest (μSBS). No statistically significant difference between (PNsi) and (PN); both showed the lowest (μSBS). Conclusion: piranha solution Surface treatment showed a comparable result to Lithium Disilicate. Whereas, nano-silica coated group showed the lowest bond strength values.