Objective: To produce broad-spectrum nanobodies (Nbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, and establish a strategy for producing Nbs broad-spectrum neutralizing the virus and its various variants. Methods: Alpacas were immunized with the receptor-binding domain (RBD) of the SARS-CoV-2 wild-type strain (WT-RBD) to construct a nanobody phage library, and the library was screened by biopanning and ELISA with the RBD of the Delta variant (Delta-RBD) to select nanobodies. The selected nanobodies were expressed and purified using the Pichia pastoris system, and their properties and functions characterized by ELISA, biolayer interferometry, pseudovirus neutralization experiments, and molecular modeling and docking. Results: The four nanobodies obtained not only have high affinity for WT-RBD, but can also effectively neutralize Delta-RBD and the RBD of the Omicron variant (Omicron-RBD). Nb34, Nb42, and Nb45 show strong binding ability to the RBD of Delta-RBD and Omicron variants, meanwhile Nb45 can effectively neutralize the pseudovirus of Omicron variants. We also found that the mechanism of these nanobodies for neutralizing SARS-CoV-2 and its variants may be related to interfering with the conserved sites on these RBD. Conclusion: The four nanobodies obtained have great potential for prevention and treatment of SARS-CoV-2 and its variants, and the strategy established in this study can also be widely used for the preparation of nanobodies broad-spectrum neutralizing viruses and their various variants.