You can either do this through a high-level "JIT API" that generates safe machine code from a validated IR (aka PNaCL), or through a fancier version of mprotect() that validates the actual machine code (aka NaCL).
In a wondrous hypothetical future where processors support a NaCL restricted operating mode, you wouldn't even need to validate; just set the processor state to thumb^Wnacl mode, and define a syscall instruction that switches to direct execution (without actually requiring a context switch to the kernel, just flip an execution flag).
This is why NaCL is so damn interesting, and JS/asm.js is not. NaCL has the possibility of turning our design of restricted execution environments on its head, in a very good (for performance) way.