Objective To analyze the regulation effect of small doses of low molecular weight heparin combined magnesium sulfate treatment on serum and placental disease-related molecules of severe preeclampsia patients. Methods Sixty-eight cases of severe preeclampsia patients between July 2012 to July 2014 in our hospital were chosen as research subjects and randomly divided into observation group and control group. The control group patients received magnesium sulfate treatment alone, the observation group patients received small doses of low molecular weight heparin combined magnesium sulfate treatment. The serum and placental levels of kallikrein expression, PAPP-A, SPI, PLGF, HPL, TGF-β1, VCAM-1 and E-selectin were compared between the two groups. Results The serum and placental kallikrein and TGF-β1 levels of the observation group were significantly higher than those of the control group (P < 0.05); while the serum and placental PAPP-A, VCAM-1 and E-selectin levels were lower than those of the control group (P < 0.05). Conclusions In severe preeclampsia patients, treatment with pancreatic kallikrein and magnesium sulfate can promote endogenous kallikrein expression, reduce the levels of gestational hypertension-related predictive factors, weaken the invasive capacity of cytotrophoblast cells.