Background and Objectives: This study aimed to investigate the relationship between the systemic immune inflammation (SII) index and the development of micro and macro complications and mortality within the first year and the following three years in type 2 diabetic retinopathy patients. Materials and Methods: The retrospective study included 523 type 2 diabetic retinopathy patients seen in the endocrinology outpatient clinic of our hospital between January and December 2019. Their demographic and clinical characteristics were analyzed using descriptive statistics. The normal distribution of quantitative data was assessed by the Shapiro–Wilk test. Mann–Whitney U, McNemar–Chi-square, and Cochran’s Q tests were used to analyze the SII values and complication rates over time. An ROC analysis determined the sensitivity and specificity of SII. A multiple linear regression analysis examined the relationship between variables and SII, while Spearman’s test assessed the correlation between CRP and SII. p < 0.05 was accepted as significant. Results: The mean age of patients was 63.5 ± 9.3 years, with mean SII values of 821.4 ± 1010.8. Higher SII values were significantly associated with acute–chronic renal failure, peripheral arterial disease, and hospitalization rates in both the first year and the following three years (p < 0.05 for all). Significant cut-off values for SII were found for micro- and macrovascular complications and death within the first year (p < 0.05 for all). The ROC curve analysis identified an optimal SII cut-off value of >594.0 for predicting near-term (1-year) complications and mortality, with a sensitivity of 73.8% and specificity of 49.4% (area under the ROC curve: 0.629, p = 0.001). Multiple linear regression indicated that smoking of at least 20 pack-years had a significant positive effect on SII. The Spearman test showed a weak positive correlation between SII and CRP. Conclusions: High SII values predict both early and late acute–chronic renal failure, peripheral arterial disease, and hospitalizations in patients with type 2 diabetic retinopathy. The study also shows that high SII values may predict microvascular and macrovascular complications of type 2 DM and mortality risk in the early period in patients with type 2 diabetic retinopathy. In addition, comorbidities and inflammatory habits, such as long-term smoking, should be considered in the clinical use of SII.