Danshen (Salvia miltiorrhiza) is an herbaceous plant widely used in the pharmaceutical industry. However, the majority of medicinal plants utilized in the US are imported, posing challenges such as fluctuations in bioactive compound concentrations and insufficient supply to meet demand. Determining the optimal plant density is a key management decision for danshen production. This study aimed to investigate the effects of different plant densities on the growth and bioactive compound content of danshen cultivated in Mississippi. A field experiment was conducted to investigate the effects of different plant densities on individual plant growth, photosynthesis, and the content of bioactive components in danshen in 2020 and 2021. Six plant densities were designed: 30 × 20 cm (between row spacing × within row spacing), 30 × 30 cm, 30 × 40 cm, 45 × 20 cm, 45 × 30 cm, or 45 × 40 cm. A plant density of 45 × 40 cm resulted in danshen plants exhibiting the highest Plant Growth Index (PGI), SPAD, root number, shoot number, shoot fresh and dry weight, maximum root diameter, maximum root length, net photosynthesis, intracellular CO2 concentration, tanshinone I, and cryptotanshinone, regardless of year. Plants spaced at 45 × 30 cm had similar root fresh weight, root dry weight, and tanshinone IIA and salvianolic acid B levels compared with plants grown at the 45 × 40 cm spacing, and both were significantly higher than other densities.