1.  Calcium Folinate is mainly used as the antidote of folic acid antagonists (such as methotrexate, pyrimethamine or trimethoprim, etc.);
2. Calcium Folinate can be used for the prevention of severe toxicity after excessive or large doses administration of methotrexate.
3.  The megaloblastic anemia caused by folic acid deficiency.
4.  In combination with fluorouracil, it is used for the treatment of advanced colon cancer and rectal cancer.
It is used for the rescue of the toxicity reaction caused by excessive amount of aminopterin and methotrexate as well as being used for the treatment of giant red blood cell anemia.
The efficacy of folate can offset the effects of folic acid antagonists. The folic acid antagonists rely on binding to folic acid dehydrogenase (DHFR), thereby preventing folate from converting to folic acid. Medically, after the chemotherapy of methotrexate, the calcium folinate can be used to reduce methotrexate toxicity. Calcium folinate can be used to enhances the cytotoxic effect of 5-fluorouracil in anticancer fields.