With the increasing demand for eco-friendly, non-petroleum-based natural rubber (NR) products, sepiolite, a naturally abundant, one-dimensional clay mineral, has been identified as a suitable material for reinforcing NR through the latex compounding method. To create superior NR/sepiolite composites, three silane coupling agents with different functional groups were used to modify sepiolite in situ via grafting or adsorption during the disaggregation and activation of natural sepiolite, which were subsequently mixed with natural rubber latex (NRL) to prepare the composites. The results showed that the modified sepiolite improved the dispersion and interfacial bonding strength with the rubber matrix. VTES-modified sepiolite containing C=C groups slightly improved the performance but retarded the vulcanization of the NR composites, and MPTES and TESPT-modified sepiolites containing -SH and −S4− groups, respectively, effectively accelerated vulcanization, inducing the composites to form a denser crosslink network structure, and exhibiting excellent dynamic and static properties, such as the modulus at a 300% increase from 8.82 MPa to 16.87 MPa, a tear strength increase from 49.6 N·mm−1 to 60.3 N·mm−1, as well as an improved rolling resistance and abrasive resistance of the composites. These findings demonstrate that modified sepiolite can be used to produce high-quality NR/sepiolite composites with enhanced properties.