Nonoptimal ambient temperatures (i.e., cold and heat) are leading environmental determinants of major diseases worldwide, but the underlying pathological mechanisms are still poorly understood. We used distributed-lag nonlinear models to examine the associations of cold (5th percentile: -2.1 °C) and heat (95th percentile: 29.5 °C) with 2923 plasma proteins in 3926 adults from 10 areas across China. Overall, 949 proteins were significantly (5% false discovery rate) associated with ambient temperature, including 387 (216/171 down/upregulated) with cold, 770 (656/114 down/upregulated) with heat, and 208 with both cold and heat. Above the median reference temperature (17.7 °C), the associations were largely linear, while below it, they were nonlinear with attenuation below 5 °C, potentially reflecting mediation by heating. Among the 949 proteins, >80% were also associated with systolic blood pressure and incident ischemic heart disease risk and enriched in relevant pathological pathways (e.g., inflammation, immunity, and platelet aggregation). Our study provided a novel atlas of plasma proteins associated with nonoptimal temperatures in Chinese adults.