The amazing thing about imagery in a text is that interpretation is left to the reader. The appearance of the lizard and snakes, in John Steinbeck's novel Of Mice and Men, can signify an abundance of things. Below are some suggestions accompanied with the text from the novel.
There are two places in the beginning of the novel when Lennie and George first arrive at the pool near the Salinas River that the creatures appear. First, the lizard makes its appearance.
On the sandy bank under the trees the leaves lie deep and so crisp that a lizard makes a great skittering if he runs among them.
Here, the lizard could signify the fact that even the insignificant weight of the lizard can cause a great noise when "skittering" over the leaves. The significance of this is that regardless of one's weight (mental (like George) or physical (like Lennie)), they will assuredly impact the things around them.
In the case of aligning the lizard with either George or Lennie, the lizard could be aligned with Lennie based upon the fact that he is unaware of what is truly around him and is unable to make conscious decisions about how heavily he trods (both literally and figuratively).
The first showing of the snake also happens in chapter one.
A water snake slipped along on the pool, its head held up like a little periscope.
Here, one can justify the significance of the water snake as the one who is conscious of its surroundings. Unlike the lizard, which makes noise, the smoothness of the snake and the description of the "periscope head" shows the direct awareness of the snake. That being said, the snake can be a mirror of George who is planning for the trouble he expects at the new ranch.
It is not until the end of the novel, when Lennie and George return to the meeting place (the pond), where the snake returns. The lizard, unfortunately, fails to return. This can be justified as foreshadowing which would symbolize the upcoming death of Lennie. The lizard can no longer simply exist unaware of the problems in life, making "a great skittering." Instead, the lizard has finally reached the end of a carefree life (if the lizard is looked at as a reflection of Lennie).
The one creature, as stated before, which makes another appearance is the snake.
A water snake glided smoothly up the pool, twisting its periscope head from side to side; and it swam the length of the pool and came to the legs of a motionless heron that stood in the shallows. A silent head and beak lanced down and plucked it out by the head, and the beak swallowed the little snake while its tail waved frantically.
Still aware of its surroundings, the snake can be, again, compared to George. George is afraid that the men, coming for Lennie's life, will be at the pond soon. The snakes periscoping mirrors George's actions. The death of the snake mirrors George's figurative death: he changes when he is forced to kill Lennie.
Soon after, another snake emerges.
Another little water snake swam up the pool, turning its periscope head from side to side.
This snake could signify the change in George. The new snake, hearing the heron pounding its wings, "slid in among the reeds at the pool’s side." This solidifies the internal change in George. While the snake, again, peers about with its "periscope head," it has a very different perspective on the dangers of life. Like the snake, George, also, has a different perspective on life.