<p>High efficiency of anti-inflammatories for anti-inflammatory drugs has enormous room for improvement, aiming to reduce side effects. Herein, molecular-modified biomimetic mesoporous silica xerogel was applied to establish a superior carrier for delivering nimesulide (NMS). Small molecules of chiral threonine and chiral malic acid, as well as a polymer of hydroxypropyl methylcellulose K250 (HPMC), were used to respectively obtain LT-MSX, DT-MSX, LM-MSX, DM-MSX, BMSX, L-BMSX, M-BMSX, and H-BMSX. Morphology and porous structure of the obtained carriers were analyzed, and properties of NMS-loaded carriers were studied by focusing on drug crystal form and molecule interactions. In vitro carrier degradation and drug release, as well as in vivo anti-inflammatory effects of drug-loaded carriers, were evaluated. The results demonstrated that the addition of molecules significantly impacted the porous properties of carriers. In addition, all these carriers improved drug release by converting the drug crystal form to an amorphous state. The swelling inhibition rate of NMS-loaded LT-MSX and NMS-loaded DT-MSX was the best, owing to their fast drug release and silica degradation, which can be of great value for the application of anti-inflammatory drugs.</p> Graphical Abstract <p></p>