Background: Insufficient kidney function increases the risk of hyperkalemia and hypoglycemia, particularly in hemodialysis-dependent patients. Hypoglycemia is a common complication of insulin-based hyperkalemia treatment. This study aims to evaluate the efficacy and safety of hyperkalemia treatment in hemodialysis-dependent and -non-dependent patients and identify risk factors associated with hypoglycemia. Methods: A retrospective observational cohort study was conducted to assess the efficacy and safety of hyperkalemia treatment including patients with reduced kidney function and hyperkalemia treated with intravenous insulin. The decline rate of potassium and glucose levels were compared between hemodialysis-dependent and non-dependent patients. In addition, univariate and multivariable logistic regression analyses were performed to identify risk factors associated with hypoglycemia. Results: A total of 172 patients with hyperkalemia and reduced kidney function were included. The steepest reduction of serum potassium levels happened within the first 6 h after insulin administration, at 1.1 and 0.9 mmol/L for hemodialysis-dependent and non-dependent patients, respectively. The incidence of hypoglycemia was 18%, and no significant difference was found between cohorts. Hemodialysis-dependent patients were more likely to be readmitted within one month with hyperkalemia, while all-cause ICU admission was more likely for non-dependent patients. Older patients, and those who had heart failure or received a second dose of insulin to treat hyperkalemia, were more likely to experience hypoglycemia. Conclusions: Monitoring blood glucose levels following insulin administration is essential given the complexity of patients’ factors associated with hypoglycemia resulting from hyperkalemia treatment in patients with insufficient kidney function.