Lithium disilicate (Li2Si2O5) glass‐ceramics are currently a more widely used all‐ceramic restorative material due to their good mechanical properties and excellent aesthetic properties. However, they have a series of problems such as high brittleness and low fracture toughness, which has become the main bottleneck restricting its development. Therefore, in order to compensate for these shortcomings, we propose to prepare a reinforced glass‐ceramics with better mechanical properties and to test the biosafety and chemical solubility of the material. Li2Si2O5 whiskers were synthesized by a one‐step hydrothermal method, and multi‐scale crystal‐enhanced Li2Si2O5 glass‐ceramics were prepared by reaction sintering. The biosafety of multi‐scale crystal‐reinforced Li2Si2O5 glass‐ceramics was investigated by in vitro cytotoxicity test, rabbit pyrogen test, mice bone marrow micronucleus test, skin sensitization test, sub‐chronic systemic toxicity test, and chronic systemic toxicity test. Additionally, the chemical solubility of multi‐scale crystal‐reinforced Li2Si2O5 glass‐ceramics was investigated. The test results showed that the material was non‐cytotoxic, non‐thermogenic, non‐mutagenic, non‐sensitizing, and non‐systemic. The chemical solubility, determined to be 377 ± 245 μg/cm2, complied with the ISO 6872 standard for the maximum solubility of ceramic materials. Multi‐scale crystal‐reinforced Li2Si2O5 glass‐ceramics' biosafety and chemical solubility met current normative criteria, and they can move on to mechanical property measurements (such as flexural strength test, fatigue life test, friction and wear property study, etc.) and bonding property optimization, which shows promise for future clinical applications.