A retrospective study analyzed the treatment of 266 pregnant women with autoimmune diseases (systemic lupus erythematosus, antiphospholipid syndrome, Sjogren's syndrome, connective tissue disease) referred to the center between 2000 and 2023. The most common therapies included low-dose aspirin, low-molecular-weight heparin (LMWH), steroids, and hydroxychloroquine (HCQ), selected according to obstetric history, antiphospholipid antibodies, and disease severity. A decline in glucocorticoid use was observed from 50% (2000–2003) to 13% (2020–2023; mean 33%, p < 0.01), associated with risks such as premature rupture of membranes, fetal growth restriction, gestational hypertension, diabetes, osteoporosis, and infections. HCQ use has increased from 13% (2000–2003) to 40% (2020–2023; mean 30%, p 0.62) and is safe for fetal development, improves pregnancy outcomes, and reduces the risk of preeclampsia and disease flares. LMWH increased slightly from 25% (2000–2003) to 61% (2020–2023; mean 50%, p 0.18). Aspirin use decreased from 100% (2000–2003) to 96% (2020–2023; mean 88%, p 0.54). These changes reflect better knowledge of the diseases and improved management for good obstetric outcomes and minimization of complications.