Insulin degludec/insulin aspart (IDegAsp) is a novel co-formulation of 70% insulin degludec and 30% insulin aspart. The present meta-analysis was conducted to assess the efficacy and safety of IDegAsp compared with a conventional premixed insulin or basal insulin. We extracted data from citation databases, including PubMed, EMBASE, and the Cochrane Library, since inception to 2021. We calculated the mean differences for hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), self-measured mean glucose, and postprandial glucose (PPG) and odds ratios for confirmed hypoglycemia events. Compared with twice-daily conventional premixed insulin, twice-daily IDegAsp showed a similar effect on changes in HbA1c, but it significantly reduced FPG and self-measured mean glucose levels. Furthermore, compared to once-daily basal insulin, once-daily IDegAsp had a similar effect on changes in HbA1c, but it significantly reduced self-measured mean glucose and PPG levels. The risk of overall confirmed hypoglycemia was similar between treatments; however, the risk of nocturnal hypoglycemia events was significantly lower with IDegAsp than with conventional premixed insulin and basal insulin. Thus, IDegAsp was more effective than conventional premixed insulin and basal insulin at reducing blood glucose with fewer nocturnal hypoglycemia events.