Despite the exceptional performance of recyclable biphasic pretreatment systems (i.e., p-toluenesulfonic acid (TsOH)/pentanol, H2SO4/butanol, and AlCl3/MTHF) in the holistic fractionation of lignocellulosic biomass (LCB), there remains a significant gap in understanding of the intricate mechanisms governing the rapid dissolution of lignin and xylan from LCB. This study conducts comparative analyses using laboratory experiments and computational simulations to gain insights into the mechanism behind removing lignin and xylan in these systems. Under identical pretreatment conditions (140 °C, 45 min), three systems exhibited distinct levels of delignification and xylan removal. TsOH/pentanol showcased the highest levels of both delignification (83.3%) and xylan removal (98.1%), followed by H2SO4/butanol (77.9% delignification and 83.0% xylan removal), and AlCl3/MTHF (73.5% delignification and 97.2% xylan removal). Lignin characterization revealed that TsOH/pentanol and AlCl3/MTHF lignin samples boasted well-preserved β-O-4 bonds (42.4/100 Ar, 40.4/100 Ar, respectively), uniform molecular weights, and <1% sugar content. This led to high yields of phenolic monomers (TsOH/pentanol, 33.9%; AlCl3/MTHF, 33.7%) after catalytic hydrogenolysis of lignin. Furthermore, mechanistic analyses revealed that the TsOH/pentanol and AlCl3/MTHF systems exhibited the most significant interaction energy formation with the lignin model (veratrylglycerol-b-guaiacyl ether) and D-xylan model due to robust hydrogen bonding interactions, yielding energy values of −2460 kJ/mol and −2385 kJ/mol, respectively. These interactions could play pivotal roles in accomplishing notable lignin and xylan extraction.