Objective The main aim of the present study was to limit contaminant microbes and their macromolecules in raw herbal drugs, then decrease TCMIs’ safety problems. Methods A raw herbal drug from underground part (Danshen, root and rhizome of Salvia miltiorrhiza Bge.) and that from aboveground part(Honghua, flower of Carthamus tinctorius L.) were introduced. The contaminant microbes were assayed at steps of the mimic process of TCMI manufacturing. Microbes adhered to raw herbal drugs Honghua or Danshen were collected, and their DNA encoded 16S rRNA(for bacteria) and 18S rRNA (for fungi) were identified by high-throughput sequencing. The feasibility of removable lipopolysaccharide(LPS) adhered to the raw drugs was investigated with TAL(Tachypleus Amebocyte Lysate) kits by detecting flushing fluid and the mimic injections. Results The results showed that both raw drugs were contaminated with microbes, and the abundance of fungi was heavier than that of bacteria. As a raw herbal drug from aerial part, Honghua contained more bacteria and fungi than Danshen. The contaminant LPS was able to be largely removed by washing. Conclusion All the results suggested that the contaminant microbes, especially fungi, and their macromolecular impurities should be taken into account for TCMI manufacturing, and they were able to be removed largely by washing.