Really depends on how many Smiths there are here. If it's around 100 or so like in the playground scene in Reloaded, then the Smiths need to start jabbing their hands in Thanos like 10 at a time to try to assimilate him. Neo was the only person that could resist Smith's assimilation, and we see (if I remember correctly) three Smiths assimilating Morpheus at once, which should speed up the process. Could work similarly to how Mantis subdued Thanos on Titan.
If Thanos' uber-durability carries over into the Matrix from the MCU "real world", the Smiths need to dog pile him big time and hope for the best with the assimilation. In a straight fight, yes I think multiple Smiths from reloaded could do damage based on their level of Matrix superhuman stats in strength, skill, and speed.
Thanos though does lots of strikes and grappling that, when combined with his size, would decimate a foe like Smith that relies more on punches and kicks. Smith comes up to Thanos to do a straight kick, Thanos grabs him and makes him a part of the concrete with a body slam.
TL;DR - Under the stips, Thanos' build and stats would make it very difficult for the Smiths to incap him through brute force, but if mass assimilation works with an accompanying stun effect on Thanos, then he gets turned into another Smith.
However, I do think Oracle-Smith from Revolutions could go toe-to-toe with Thanos: strong enough to pile up concrete behind him after getting punched into it with no ill effect, plenty faster than Thanos, can fly, etc.