Wastewater reclamation and reuse for agriculture have attracted a great deal of interest, due to water stress caused by rapid increase in human population and agricultural water demand as well as climate change. However, the application of treated wastewater for irrigation can lead to the accumulation of pharmaceuticals and personal care products (PPCPs) in the agricultural crops, grazing animals, and consequently to human dietary exposure. In this study, a model was developed to simulate the fate of five PPCPs; triclosan (TCS), carbamazepine (CBZ), naproxen (NPX), gemfibrozil (GFB), and fluoxetine (FXT) during wastewater reuse for agriculture, and potential human dietary exposure and health risk. In a reclaimed wastewater-irrigated grazing farm growing alfalfa, it took 100–535 days for PPCPs to achieve the steady-state concentrations of 1.43 × 10−6, 4.73 × 10−5, 1.17 × 10−6, 1.53 × 10−5, and 7.38 × 10−6 mg/kg for TCS, CBZ, NPX, GFB, and FXT in soils, respectively. The accumulated concentration of PPCPs in the plant (alfalfa) and grazing animals (beef) ranged 2.86 × 10−7− 4.02 × 10−3 and 4.39 × 10−15− 6.27 × 10−7 mg/kg, respectively. Human dietary exposure to these compounds through beef consumption was calculated to be 1.67 × 10−18− 1.74 × 10−10 mg/kg bodyweight/d, much lower than the acceptable daily intake (ADI). Similar results were obtained for a ‘typical’ reclaimed wastewater irrigated farm based on the typical setup using our model. Screening analysis showed that PPCPs with relatively high LogD value and lower ratios of degradation rate (in soils) to plant uptake have a greater potential to be transferred to humans and cause potential health risks. We established a modeling method for evaluating the fate and human health effects of PPCPs in reclaimed wastewater reuse for the agricultural system and developed an index for screening PPCPs with high potential to accumulate in agricultural products. The model and findings are valuable for managing water reuse for irrigation and mitigating the harmful effects of PPCPs.