Patients with primary nephrotic syndrome (PNS) are at an increased risk of developing various infections due to the long-term use of immunosuppressive agents. Cryptococcal meningitis (CM) is an uncommon but severe complication that can occur in patients with PNS, particularly those receiving immunosuppressive medications. This case report describes a middle-aged female patient with PNS and type 2 diabetes mellitus (T2DM) who developed CM. She received a combination regimen of cyclophosphamide and prednisone, achieving partial remission of PNS. However, she later returned to the hospital with high fever and headache. At admission, her nasopharyngeal swab test was positive for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and she received therapy of dexamethasone and favipiravir, but her fever and headache were not improved. Following a lumbar puncture was performed for her and CM was diagnosed based on a positive Cryptococcus culture in the cerebrospinal fluid. The patient's cyclophosphamides were temporarily discontinued, and antifungal therapy with amphotericin B liposome and fluconazole was initiated. Despite a noticeable increase in her blood glucose levels due to infection during her hospitalization, she showed improvement with intensified glycemic control treatment. The anti-infection showed significant effectiveness, and the patient's proteinuria remained stable during follow-up. The patient with PNS and T2DM was concurrently diagnosed with both CM and coronavirus disease 2019 (COVID-19), marking the first reported case of such co-infections in these patients. Prompt diagnosis and appropriate antifungal therapy are crucial for improved outcomes of PNS patients with CM and COVID-19.