We investigated the suitability of dithiocarbamate (DTC) capped Ag nanoparticles (NPs) as resonance light scattering (RLS) probes for the simultaneous sensing of Pb(2+) and cysteine. The DTC capping ligands are generated by a very simple in situ method through reaction of carbon disulfide with diethanolamine as primary precursor molecules under ultrasonic irradiation. This strategy was based on the fact that Pb(2+) could induce the aggregation of DTC-Ag NPs due to the strong metal affinity of DTC along with an enhanced RLS signal. After optimizing some experimental conditions (including the pH value of the solution, concentration of DTC-Ag NPs, and ion strength), a very simple and facile sensing system has been developed for the detection of Pb(2+) in water based on RLS technology. The proposed system promises excellent selectivity, a wide linear response range and high sensitivity for Pb(2+). The linear response range for Pb(2+) was from 0.01 μM to 60 μM. The limit of detection (S/N = 3σ) for Pb(2+) was as low as 4 nM. The proposed method was successfully used to detect Pb(2+) in river and tap water samples, indicating the potential of this new, sensitive and selective method in water quality monitoring. Meanwhile, due to the strong binding preference of cysteine toward Pb(2+) by the formation of Pb(2+)-S bonds, Pb(2+) was removed from the surfaces of the DTC-Ag NPs, leading to redispersion of DTC-Ag NPs, along with a decreased RLS signal. The possibility of the proposed system for the sensing of cysteine was also investigated.