The drug loading capacity is a critical performance metric for drug delivery systems. A high capacity ensures efficient drug delivery to target sites at lower doses, reducing the amount of carrier material needed and lessening patient burden. However, improving drug loading capacity in diatom frustule-based systems remains a challenge. In this study, we explored effective strategies for developing a microcarrier with a high drug loading efficiency using diatom frustules (DF) derived from Thalassiosira weissflogii. We found that combining an evaporative loading method with a chitosan (Chi) coating was particularly effective for enhancing the drug loading capacity of indomethacin (IND), a hydrophobic model drug. Further optimization of the indomethacin-to-APTES-modified frustule (DF-NH) ratio to 2:1, along with adjusting the medium pH to 5, further improved drug loading efficiency. Additionally, the chitosan coating on the drug-loaded frustules not only enabled sustained drug release but also enhanced the biocompatibility of the carriers. The resulting DF-NH/IND@Chi microcarrier demonstrated a drug loading efficiency of 58.78 ± 1.92 % for IND, with a pH-dependent controlled release profile. This performance significantly outperforms previous reports, which typically report loading efficiencies between 10 % and 35 %, with few exceeding 40 %. In vitro cytotoxicity tests also revealed significant activity against colon cancer cells, highlighting the potential therapeutic benefits of this system. This study provides a systematic approach to creating high-capacity drug microcarriers using diatom frustules, offering promising prospects for future drug delivery applications.