This research, for the first time, obtained and reported three novel Form I, Form II, and Form III of 20(R)-25-methoxyl-dammarane-3β,12β,20-triol polymorphs, which were distinguished by PXRD, IR, DSC, and SEM. This study firstly exploited a rapid and feasible UHPLC-ESI-MS/MS method to determine plasma levels of 20(R)-25-OCH3-PPD within 4.5 min. The composition of mobile phase was acetonitrile and 5 mM ammonium acetate water (85:15, v/v) at a flow rate of 0.2 mL/min on the BEH C18 Column (2.1 mm × 50 mm, 1.7 μm). The approach enhanced the efficiency of analysis compared to reported methods, making a 3-fold reduction in runtimes. The research exhibited that optimal crystal Form I displays higher bioavailability (P < 0.05) compared to the other crystal forms. These findings hold great significance in the early research stages of 20(R)-25-OCH3-PPD polymorphs.